A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
Ribonucleic acid that makes up the genetic material of viruses.
A process that changes the nucleotide sequence of mRNA from that of the DNA template encoding it. Some major classes of RNA editing are as follows: 1, the conversion of cytosine to uracil in mRNA; 2, the addition of variable number of guanines at pre-determined sites; and 3, the addition and deletion of uracils, templated by guide-RNAs (RNA, GUIDE).
The ultimate exclusion of nonsense sequences or intervening sequences (introns) before the final RNA transcript is sent to the cytoplasm.
The most abundant form of RNA. Together with proteins, it forms the ribosomes, playing a structural role and also a role in ribosomal binding of mRNA and tRNAs. Individual chains are conventionally designated by their sedimentation coefficients. In eukaryotes, four large chains exist, synthesized in the nucleolus and constituting about 50% of the ribosome. (Dorland, 28th ed)
Ribonucleic acid in bacteria having regulatory and catalytic roles as well as involvement in protein synthesis.
Enzymes that catalyze DNA template-directed extension of the 3'-end of an RNA strand one nucleotide at a time. They can initiate a chain de novo. In eukaryotes, three forms of the enzyme have been distinguished on the basis of sensitivity to alpha-amanitin, and the type of RNA synthesized. (From Enzyme Nomenclature, 1992).
Viruses whose genetic material is RNA.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
RNA consisting of two strands as opposed to the more prevalent single-stranded RNA. Most of the double-stranded segments are formed from transcription of DNA by intramolecular base-pairing of inverted complementary sequences separated by a single-stranded loop. Some double-stranded segments of RNA are normal in all organisms.
RNA that has catalytic activity. The catalytic RNA sequence folds to form a complex surface that can function as an enzyme in reactions with itself and other molecules. It may function even in the absence of protein. There are numerous examples of RNA species that are acted upon by catalytic RNA, however the scope of this enzyme class is not limited to a particular type of substrate.
The processes of RNA tertiary structure formation.
A DNA-dependent RNA polymerase present in bacterial, plant, and animal cells. It functions in the nucleoplasmic structure and transcribes DNA into RNA. It has different requirements for cations and salt than RNA polymerase I and is strongly inhibited by alpha-amanitin. EC 2.7.7.6.
Ribonucleic acid in fungi having regulatory and catalytic roles as well as involvement in protein synthesis.
The extent to which an RNA molecule retains its structural integrity and resists degradation by RNASE, and base-catalyzed HYDROLYSIS, under changing in vivo or in vitro conditions.
A family of proteins that promote unwinding of RNA during splicing and translation.
RNA molecules which hybridize to complementary sequences in either RNA or DNA altering the function of the latter. Endogenous antisense RNAs function as regulators of gene expression by a variety of mechanisms. Synthetic antisense RNAs are used to effect the functioning of specific genes for investigative or therapeutic purposes.
Post-transcriptional biological modification of messenger, transfer, or ribosomal RNAs or their precursors. It includes cleavage, methylation, thiolation, isopentenylation, pseudouridine formation, conformational changes, and association with ribosomal protein.
The small RNA molecules, 73-80 nucleotides long, that function during translation (TRANSLATION, GENETIC) to align AMINO ACIDS at the RIBOSOMES in a sequence determined by the mRNA (RNA, MESSENGER). There are about 30 different transfer RNAs. Each recognizes a specific CODON set on the mRNA through its own ANTICODON and as aminoacyl tRNAs (RNA, TRANSFER, AMINO ACYL), each carries a specific amino acid to the ribosome to add to the elongating peptide chains.
Short chains of RNA (100-300 nucleotides long) that are abundant in the nucleus and usually complexed with proteins in snRNPs (RIBONUCLEOPROTEINS, SMALL NUCLEAR). Many function in the processing of messenger RNA precursors. Others, the snoRNAs (RNA, SMALL NUCLEOLAR), are involved with the processing of ribosomal RNA precursors.
RNA transcripts of the DNA that are in some unfinished stage of post-transcriptional processing (RNA PROCESSING, POST-TRANSCRIPTIONAL) required for function. RNA precursors may undergo several steps of RNA SPLICING during which the phosphodiester bonds at exon-intron boundaries are cleaved and the introns are excised. Consequently a new bond is formed between the ends of the exons. Resulting mature RNAs can then be used; for example, mature mRNA (RNA, MESSENGER) is used as a template for protein production.
RNA which does not code for protein but has some enzymatic, structural or regulatory function. Although ribosomal RNA (RNA, RIBOSOMAL) and transfer RNA (RNA, TRANSFER) are also untranslated RNAs they are not included in this scope.
The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.
Nucleic acid structures found on the 5' end of eukaryotic cellular and viral messenger RNA and some heterogeneous nuclear RNAs. These structures, which are positively charged, protect the above specified RNAs at their termini against attack by phosphatases and other nucleases and promote mRNA function at the level of initiation of translation. Analogs of the RNA caps (RNA CAP ANALOGS), which lack the positive charge, inhibit the initiation of protein synthesis.
A multistage process that includes cloning, physical mapping, subcloning, sequencing, and information analysis of an RNA SEQUENCE.
Ribonucleic acid in plants having regulatory and catalytic roles as well as involvement in protein synthesis.
Ribonucleic acid in protozoa having regulatory and catalytic roles as well as involvement in protein synthesis.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
RNA present in neoplastic tissue.
An enzyme that catalyzes the conversion of linear RNA to a circular form by the transfer of the 5'-phosphate to the 3'-hydroxyl terminus. It also catalyzes the covalent joining of two polyribonucleotides in phosphodiester linkage. EC 6.5.1.3.
A large family of RNA helicases that share a common protein motif with the single letter amino acid sequence D-E-A-D (Asp-Glu-Ala-Asp). In addition to RNA helicase activity, members of the DEAD-box family participate in other aspects of RNA metabolism and regulation of RNA function.
A DNA-dependent RNA polymerase present in bacterial, plant, and animal cells. It functions in the nucleoplasmic structure where it transcribes DNA into RNA. It has specific requirements for cations and salt and has shown an intermediate sensitivity to alpha-amanitin in comparison to RNA polymerase I and II. EC 2.7.7.6.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A DNA-dependent RNA polymerase present in bacterial, plant, and animal cells. The enzyme functions in the nucleolar structure and transcribes DNA into RNA. It has different requirements for cations and salts than RNA polymerase II and III and is not inhibited by alpha-amanitin. EC 2.7.7.6.
RNA molecules found in the nucleus either associated with chromosomes or in the nucleoplasm.
Small kinetoplastid mitochondrial RNA that plays a major role in RNA EDITING. These molecules form perfect hybrids with edited mRNA sequences and possess nucleotide sequences at their 5'-ends that are complementary to the sequences of the mRNA's immediately downstream of the pre-edited regions.
Constituent of the 60S subunit of eukaryotic ribosomes. 28S rRNA is involved in the initiation of polypeptide synthesis in eukaryotes.
Constituent of the 40S subunit of eukaryotic ribosomes. 18S rRNA is involved in the initiation of polypeptide synthesis in eukaryotes.
Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA.
Constituent of 50S subunit of prokaryotic ribosomes containing about 3200 nucleotides. 23S rRNA is involved in the initiation of polypeptide synthesis.
The process of moving specific RNA molecules from one cellular compartment or region to another by various sorting and transport mechanisms.
The small RNAs which provide spliced leader sequences, SL1, SL2, SL3, SL4 and SL5 (short sequences which are joined to the 5' ends of pre-mRNAs by TRANS-SPLICING). They are found primarily in primitive eukaryotes (protozoans and nematodes).
Small, linear single-stranded RNA molecules functionally acting as molecular parasites of certain RNA plant viruses. Satellite RNAs exhibit four characteristic traits: (1) they require helper viruses to replicate; (2) they are unnecessary for the replication of helper viruses; (3) they are encapsidated in the coat protein of the helper virus; (4) they have no extensive sequence homology to the helper virus. Thus they differ from SATELLITE VIRUSES which encode their own coat protein, and from the genomic RNA; (=RNA, VIRAL); of satellite viruses. (From Maramorosch, Viroids and Satellites, 1991, p143)
Constituent of 30S subunit prokaryotic ribosomes containing 1600 nucleotides and 21 proteins. 16S rRNA is involved in initiation of polypeptide synthesis.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Ribonucleic acid in archaea having regulatory and catalytic roles as well as involvement in protein synthesis.
Widely used technique which exploits the ability of complementary sequences in single-stranded DNAs or RNAs to pair with each other to form a double helix. Hybridization can take place between two complimentary DNA sequences, between a single-stranded DNA and a complementary RNA, or between two RNA sequences. The technique is used to detect and isolate specific sequences, measure homology, or define other characteristics of one or both strands. (Kendrew, Encyclopedia of Molecular Biology, 1994, p503)
The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS.
Established cell cultures that have the potential to propagate indefinitely.
The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
A reaction that severs one of the sugar-phosphate linkages of the phosphodiester backbone of RNA. It is catalyzed enzymatically, chemically, or by radiation. Cleavage may be exonucleolytic, or endonucleolytic.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
A group of ribonucleotides (up to 12) in which the phosphate residues of each ribonucleotide act as bridges in forming diester linkages between the ribose moieties.
Nuclear nonribosomal RNA larger than about 1000 nucleotides, the mass of which is rapidly synthesized and degraded within the cell nucleus. Some heterogeneous nuclear RNA may be a precursor to mRNA. However, the great bulk of total hnRNA hybridizes with nuclear DNA rather than with mRNA.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
Small RNAs found in the cytoplasm usually complexed with proteins in scRNPs (RIBONUCLEOPROTEINS, SMALL CYTOPLASMIC).
The steps that generate the 3' ends of mature RNA molecules. For most mRNAs (RNA, MESSENGER), 3' end processing referred to as POLYADENYLATION includes the addition of POLY A.
Macromolecular molds for the synthesis of complementary macromolecules, as in DNA REPLICATION; GENETIC TRANSCRIPTION of DNA to RNA, and GENETIC TRANSLATION of RNA into POLYPEPTIDES.
Short RNA, about 200 base pairs in length or shorter, that does not code for protein.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
Complexes of RNA-binding proteins with ribonucleic acids (RNA).
Enzymes that catalyze the hydrolysis of ester bonds within RNA. EC 3.1.-.
A group of adenine ribonucleotides in which the phosphate residues of each adenine ribonucleotide act as bridges in forming diester linkages between the ribose moieties.
The complete genetic complement contained in a DNA or RNA molecule in a virus.
Constituent of the 60S subunit of eukaryotic ribosomes. 5.8S rRNA is involved in the initiation of polypeptide synthesis in eukaryotes.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
A class of untranslated RNA molecules that are typically greater than 200 nucleotides in length and do not code for proteins. Members of this class have been found to play roles in transcriptional regulation, post-transcriptional processing, CHROMATIN REMODELING, and in the epigenetic control of chromatin.
Small nuclear RNAs that are involved in the processing of pre-ribosomal RNA in the nucleolus. Box C/D containing snoRNAs (U14, U15, U16, U20, U21 and U24-U63) direct site-specific methylation of various ribose moieties. Box H/ACA containing snoRNAs (E2, E3, U19, U23, and U64-U72) direct the conversion of specific uridines to pseudouridine. Site-specific cleavages resulting in the mature ribosomal RNAs are directed by snoRNAs U3, U8, U14, U22 and the snoRNA components of RNase MRP and RNase P.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Synthetic transcripts of a specific DNA molecule or fragment, made by an in vitro transcription system. This cRNA can be labeled with radioactive uracil and then used as a probe. (King & Stansfield, A Dictionary of Genetics, 4th ed)
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
A family of enzymes that catalyze the endonucleolytic cleavage of RNA. It includes EC 3.1.26.-, EC 3.1.27.-, EC 3.1.30.-, and EC 3.1.31.-.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
Ribonucleic acid in chloroplasts having regulatory and catalytic roles as well as involvement in protein synthesis.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
The rate dynamics in chemical or physical systems.
Enzymes that catalyze the endonucleolytic cleavage of single-stranded regions of DNA or RNA molecules while leaving the double-stranded regions intact. They are particularly useful in the laboratory for producing "blunt-ended" DNA molecules from DNA with single-stranded ends and for sensitive GENETIC TECHNIQUES such as NUCLEASE PROTECTION ASSAYS that involve the detection of single-stranded DNA and RNA.
Pairing of purine and pyrimidine bases by HYDROGEN BONDING in double-stranded DNA or RNA.
Ribonucleic acid in helminths having regulatory and catalytic roles as well as involvement in protein synthesis.
Viruses parasitic on plants higher than bacteria.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
A transfer RNA which is specific for carrying phenylalanine to sites on the ribosomes in preparation for protein synthesis.
A transfer RNA which is specific for carrying lysine to sites on the ribosomes in preparation for protein synthesis.
Multicomponent ribonucleoprotein structures found in the CYTOPLASM of all cells, and in MITOCHONDRIA, and PLASTIDS. They function in PROTEIN BIOSYNTHESIS via GENETIC TRANSLATION.
Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
Deoxyribonucleic acid that makes up the genetic material of viruses.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
Polymers made up of a few (2-20) nucleotides. In molecular genetics, they refer to a short sequence synthesized to match a region where a mutation is known to occur, and then used as a probe (OLIGONUCLEOTIDE PROBES). (Dorland, 28th ed)
Interruption or suppression of the expression of a gene at transcriptional or translational levels.
The sequence at the 5' end of the messenger RNA that does not code for product. This sequence contains the ribosome binding site and other transcription and translation regulating sequences.
A transfer RNA which is specific for carrying tyrosine to sites on the ribosomes in preparation for protein synthesis.
The sequential correspondence of nucleotides in one nucleic acid molecule with those of another nucleic acid molecule. Sequence homology is an indication of the genetic relatedness of different organisms and gene function.
The sequence at the 3' end of messenger RNA that does not code for product. This region contains transcription and translation regulating sequences.
Cyclic peptides extracted from carpophores of various mushroom species. They are potent inhibitors of RNA polymerases in most eukaryotic species, blocking the production of mRNA and protein synthesis. These peptides are important in the study of transcription. Alpha-amanitin is the main toxin from the species Amanitia phalloides, poisonous if ingested by humans or animals.
The functional hereditary units of VIRUSES.
Disruption of the secondary structure of nucleic acids by heat, extreme pH or chemical treatment. Double strand DNA is "melted" by dissociation of the non-covalent hydrogen bonds and hydrophobic interactions. Denatured DNA appears to be a single-stranded flexible structure. The effects of denaturation on RNA are similar though less pronounced and largely reversible.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
An enzyme catalyzing the endonucleolytic cleavage of RNA at the 3'-position of a guanylate residue. EC 3.1.27.3.
The sum of the weight of all the atoms in a molecule.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
Within most types of eukaryotic CELL NUCLEUS, a distinct region, not delimited by a membrane, in which some species of rRNA (RNA, RIBOSOMAL) are synthesized and assembled into ribonucleoprotein subunits of ribosomes. In the nucleolus rRNA is transcribed from a nucleolar organizer, i.e., a group of tandemly repeated chromosomal genes which encode rRNA and which are transcribed by RNA polymerase I. (Singleton & Sainsbury, Dictionary of Microbiology & Molecular Biology, 2d ed)
The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.
A fractionated cell extract that maintains a biological function. A subcellular fraction isolated by ultracentrifugation or other separation techniques must first be isolated so that a process can be studied free from all of the complex side reactions that occur in a cell. The cell-free system is therefore widely used in cell biology. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p166)
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.
Any of the processes by which cytoplasmic factors influence the differential control of gene action in viruses.
A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.
A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a CONSENSUS SEQUENCE. AMINO ACID MOTIFS are often composed of conserved sequences.
Proteins encoded by a VIRAL GENOME that are produced in the organisms they infect, but not packaged into the VIRUS PARTICLES. Some of these proteins may play roles within the infected cell during VIRUS REPLICATION or act in regulation of virus replication or VIRUS ASSEMBLY.
Intermediates in protein biosynthesis. The compounds are formed from amino acids, ATP and transfer RNA, a reaction catalyzed by aminoacyl tRNA synthetase. They are key compounds in the genetic translation process.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Sequences of DNA in the genes that are located between the EXONS. They are transcribed along with the exons but are removed from the primary gene transcript by RNA SPLICING to leave mature RNA. Some introns code for separate genes.
Nucleotide sequences located at the ends of EXONS and recognized in pre-messenger RNA by SPLICEOSOMES. They are joined during the RNA SPLICING reaction, forming the junctions between exons.
A transfer RNA which is specific for carrying alanine to sites on the ribosomes in preparation for protein synthesis.
A species of ENTEROVIRUS which is the causal agent of POLIOMYELITIS in humans. Three serotypes (strains) exist. Transmission is by the fecal-oral route, pharyngeal secretions, or mechanical vector (flies). Vaccines with both inactivated and live attenuated virus have proven effective in immunizing against the infection.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A plant genus of the family SOLANACEAE. Members contain NICOTINE and other biologically active chemicals; its dried leaves are used for SMOKING.
An RNA-containing enzyme that plays an essential role in tRNA processing by catalyzing the endonucleolytic cleavage of TRANSFER RNA precursors. It removes the extra 5'-nucleotides from tRNA precursors to generate mature tRNA molecules.
Separation of particles according to density by employing a gradient of varying densities. At equilibrium each particle settles in the gradient at a point equal to its density. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)
The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed)
Viruses which produce a mottled appearance of the leaves of plants.
An enzyme that synthesizes DNA on an RNA template. It is encoded by the pol gene of retroviruses and by certain retrovirus-like elements. EC 2.7.7.49.
A compound composed of a two CYCLIC PEPTIDES attached to a phenoxazine that is derived from STREPTOMYCES parvullus. It binds to DNA and inhibits RNA synthesis (transcription), with chain elongation more sensitive than initiation, termination, or release. As a result of impaired mRNA production, protein synthesis also declines after dactinomycin therapy. (From AMA Drug Evaluations Annual, 1993, p2015)
A sequence of successive nucleotide triplets that are read as CODONS specifying AMINO ACIDS and begin with an INITIATOR CODON and end with a stop codon (CODON, TERMINATOR).
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
A genus of FLAVIVIRIDAE causing parenterally-transmitted HEPATITIS C which is associated with transfusions and drug abuse. Hepatitis C virus is the type species.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
A transfer RNA which is specific for carrying aspartic acid to sites on the ribosomes in preparation for protein synthesis.
A transfer RNA which is specific for carrying methionine to sites on the ribosomes. During initiation of protein synthesis, tRNA(f)Met in prokaryotic cells and tRNA(i)Met in eukaryotic cells binds to the start codon (CODON, INITIATOR).
The relationships of groups of organisms as reflected by their genetic makeup.
A genus of tripartite plant viruses in the family BROMOVIRIDAE. Transmission is by beetles. Brome mosaic virus is the type species.
Proteins prepared by recombinant DNA technology.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
A ribonuclease that specifically cleaves the RNA moiety of RNA:DNA hybrids. It has been isolated from a wide variety of prokaryotic and eukaryotic organisms as well as RETROVIRUSES.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.
Sequences within RNA that regulate the processing, stability (RNA STABILITY) or translation (TRANSLATION, GENETIC) of RNA.
A multiribosomal structure representing a linear array of RIBOSOMES held together by messenger RNA; (RNA, MESSENGER); They represent the active complexes in cellular protein synthesis and are able to incorporate amino acids into polypeptides both in vivo and in vitro. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
A cell line derived from cultured tumor cells.
The outer protein protective shell of a virus, which protects the viral nucleic acid.
A family of enzymes that catalyze the exonucleolytic cleavage of RNA. It includes EC 3.1.13.-, EC 3.1.14.-, EC 3.1.15.-, and EC 3.1.16.-. EC 3.1.-
The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.
Proteins found in any species of bacterium.
Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.
A transfer RNA which is specific for carrying glycine to sites on the ribosomes in preparation for protein synthesis.
A transfer RNA which is specific for carrying histidine to sites on the ribosomes in preparation for protein synthesis.
Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.
A transfer RNA which is specific for carrying valine to sites on the ribosomes in preparation for protein synthesis.
A group of uridine ribonucleotides in which the phosphate residues of each uridine ribonucleotide act as bridges in forming diester linkages between the ribose moieties.
A family of RNA viruses infecting insects and fish. There are two genera: Alphanodavirus and Betanodavirus.
Use for nucleic acid precursors in general or for which there is no specific heading.
The assembly of VIRAL STRUCTURAL PROTEINS and nucleic acid (VIRAL DNA or VIRAL RNA) to form a VIRUS PARTICLE.
Viruses which lack a complete genome so that they cannot completely replicate or cannot form a protein coat. Some are host-dependent defectives, meaning they can replicate only in cell systems which provide the particular genetic function which they lack. Others, called SATELLITE VIRUSES, are able to replicate only when their genetic defect is complemented by a helper virus.
Deletion of sequences of nucleic acids from the genetic material of an individual.
A transfer RNA which is specific for carrying arginine to sites on the ribosomes in preparation for protein synthesis.
Ribonucleic acid in algae having regulatory and catalytic roles as well as involvement in protein synthesis.
A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.
A family of ribonucleoproteins that were originally found as proteins bound to nascent RNA transcripts in the form of ribonucleoprotein particles. Although considered ribonucleoproteins they are primarily classified by their protein component. They are involved in a variety of processes such as packaging of RNA and RNA TRANSPORT within the nucleus. A subset of heterogeneous-nuclear ribonucleoproteins are involved in additional functions such as nucleocytoplasmic transport (ACTIVE TRANSPORT, CELL NUCLEUS) of RNA and mRNA stability in the CYTOPLASM.
Proteins obtained from ESCHERICHIA COLI.
The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.
A process whereby multiple RNA transcripts are generated from a single gene. Alternative splicing involves the splicing together of other possible sets of EXONS during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form a mature RNA. The alternative forms of mature MESSENGER RNA produce PROTEIN ISOFORMS in which one part of the isoforms is common while the other parts are different.
The infective system of a virus, composed of the viral genome, a protein core, and a protein coat called a capsid, which may be naked or enclosed in a lipoprotein envelope called the peplos.
Highly conserved nuclear RNA-protein complexes that function in RNA processing in the nucleus, including pre-mRNA splicing and pre-mRNA 3'-end processing in the nucleoplasm, and pre-rRNA processing in the nucleolus (see RIBONUCLEOPROTEINS, SMALL NUCLEOLAR).
A defective virus, containing particles of RNA nucleoprotein in virion-like form, present in patients with acute hepatitis B and chronic hepatitis. It requires the presence of a hepadnavirus for full replication. This is the lone species in the genus Deltavirus.
Proteins found in ribosomes. They are believed to have a catalytic function in reconstituting biologically active ribosomal subunits.
A transfer RNA which is specific for carrying tryptophan to sites on the ribosomes in preparation for protein synthesis.
Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING.
DNA sequences recognized as signals to end GENETIC TRANSCRIPTION.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.
Multicellular, eukaryotic life forms of kingdom Plantae (sensu lato), comprising the VIRIDIPLANTAE; RHODOPHYTA; and GLAUCOPHYTA; all of which acquired chloroplasts by direct endosymbiosis of CYANOBACTERIA. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (MERISTEMS); cellulose within cells providing rigidity; the absence of organs of locomotion; absence of nervous and sensory systems; and an alternation of haploid and diploid generations.
Elements of limited time intervals, contributing to particular results or situations.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.
A bacteriophage genus of the family LEVIVIRIDAE, whose viruses contain the short version of the genome and have a separate gene for cell lysis.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
A hemoflagellate subspecies of parasitic protozoa that causes nagana in domestic and game animals in Africa. It apparently does not infect humans. It is transmitted by bites of tsetse flies (Glossina).
Enzymes that are part of the restriction-modification systems. They catalyze the endonucleolytic cleavage of DNA sequences which lack the species-specific methylation pattern in the host cell's DNA. Cleavage yields random or specific double-stranded fragments with terminal 5'-phosphates. The function of restriction enzymes is to destroy any foreign DNA that invades the host cell. Most have been studied in bacterial systems, but a few have been found in eukaryotic organisms. They are also used as tools for the systematic dissection and mapping of chromosomes, in the determination of base sequences of DNAs, and have made it possible to splice and recombine genes from one organism into the genome of another. EC 3.21.1.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.
Any of the processes by which cytoplasmic or intercellular factors influence the differential control of gene action in bacteria.
A genus of plant viruses that infects ANGIOSPERMS. Transmission occurs mechanically and through soil, with one species transmitted via a fungal vector. The type species is Tomato bushy stunt virus.
A purine nucleoside that has guanine linked by its N9 nitrogen to the C1 carbon of ribose. It is a component of ribonucleic acid and its nucleotides play important roles in metabolism. (From Dorland, 28th ed)
The addition of a tail of polyadenylic acid (POLY A) to the 3' end of mRNA (RNA, MESSENGER). Polyadenylation involves recognizing the processing site signal, (AAUAAA), and cleaving of the mRNA to create a 3' OH terminal end to which poly A polymerase (POLYNUCLEOTIDE ADENYLYLTRANSFERASE) adds 60-200 adenylate residues. The 3' end processing of some messenger RNAs, such as histone mRNA, is carried out by a different process that does not include the addition of poly A as described here.
A transfer RNA which is specific for carrying leucine to sites on the ribosomes in preparation for protein synthesis.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. (From Stedman, 25th ed)

A novel nucleotide incorporation activity implicated in the editing of mitochondrial transfer RNAs in Acanthamoeba castellanii. (1/1357)

In Acanthamoeba castellanii, most of the mtDNA-encoded tRNAs are edited by a process that replaces one or more of the first three nucleotides at their 5' ends. As a result, base pairing potential is restored at acceptor stem positions (1:72, 2:71, and/or 3:70, in standard tRNA nomenclature) that are mismatched according to the corresponding tRNA gene sequence. Here we describe a novel nucleotide incorporation activity, partially purified from A. castellanii mitochondria, that has properties implicating it in mitochondrial tRNA editing in this organism. This activity is able to replace nucleotides at the first three positions of a tRNA (positions 1, 2, and 3), matching the newly incorporated residues through canonical base pairing to the respective partner nucleotide in the 3' half of the acceptor stem. Labeling experiments with natural (Escherichia coli tRNATyr) and synthetic (run-off transcripts corresponding to A. castellanii mitochondrial tRNALeu1) substrates suggest that the nucleotide incorporation activity consists of at least two components, a 5' exonuclease or endonuclease and a template-directed 3'-to-5' nucleotidyltransferase. The nucleotidyltransferase component displays an ATP requirement and generates 5' pppN... termini in vitro. The development of an accurate and efficient in vitro system opens the way for detailed studies of the biochemical properties of this novel activity and its relationship to mitochondrial tRNA editing in A. castellanii. In addition, the system will allow delineation of the structural features in a tRNA that identify it as a substrate for the labeling activity.  (+info)

A cis-acting A-U sequence element induces kinetoplastid U-insertions. (2/1357)

A 34-nucleotide A-U sequence located immediately upstream of the editing sites of the Leishmania tarentolae cytochrome b mRNA induces a mitochondrial extract to insert U nucleotides independent of guide RNA. Insertions are localized to positions immediately 5' and 3' of the A-U sequence. When placed within an unedited mammalian transcript, the A-U sequence is sufficient to induce U-insertions. The sequence has a high degree of similarity with the templating nucleotides of a cytochrome b guide RNA and with a sequence adjacent to the editing sites in ND7 mRNA, the other characterized kinetoplastid mRNA supporting guide RNA-independent U-insertions. At least one protein specifically interacts with the A-U sequence. The reaction is consistent with a mechanism proposed for guide RNA-directed editing.  (+info)

The RNA-editing enzyme ADAR1 is localized to the nascent ribonucleoprotein matrix on Xenopus lampbrush chromosomes but specifically associates with an atypical loop. (3/1357)

Double-stranded RNA adenosine deaminase (ADAR1, dsRAD, DRADA) converts adenosines to inosines in double-stranded RNAs. Few candidate substrates for ADAR1 editing are known at this point and it is not known how substrate recognition is achieved. In some cases editing sites are defined by basepaired regions formed between intronic and exonic sequences, suggesting that the enzyme might function cotranscriptionally. We have isolated two variants of Xenopus laevis ADAR1 for which no editing substrates are currently known. We demonstrate that both variants of the enzyme are associated with transcriptionally active chromosome loops suggesting that the enzyme acts cotranscriptionally. The widespread distribution of the protein along the entire chromosome indicates that ADAR1 associates with the RNP matrix in a substrate-independent manner. Inhibition of splicing, another cotranscriptional process, does not affect the chromosomal localization of ADAR1. Furthermore, we can show that the enzyme is dramatically enriched on a special RNA-containing loop that seems transcriptionally silent. Detailed analysis of this loop suggests that it might represent a site of ADAR1 storage or a site where active RNA editing is taking place. Finally, mutational analysis of ADAR1 demonstrates that a putative Z-DNA binding domain present in ADAR1 is not required for chromosomal targeting of the protein.  (+info)

The involvement of gRNA-binding protein gBP21 in RNA editing-an in vitro and in vivo analysis. (4/1357)

RNA editing in the parasitic organism Trypanosoma brucei is characterised by the insertion and deletion of uridylate residues into otherwise incomplete primary transcripts. The processing reaction is a required pathway for the expression of most mitochondrial genes and proceeds by a cascade of enzyme-catalysed steps. RNA editing involves one or more macromolecular ribonucleoprotein complexes which are likely to interact with additional components as the reaction proceeds. Here we examined the involvement of the gRNA-binding polypeptide gBP21, a protein which has been demonstrated to be associated with active RNA editing complexes. We show that in vitro RNA editing can be suppressed by the addition of a gBP21-specific antibody or by immunodepletion of the protein. By creating a gBP21 knockout mutant we analysed the requirement for the protein in vivo. gBP21(-) trypanosomes are viable as bloodstream stage cells and contain edited mRNAs. However, the knockout mutant is not capable of differentiating from the bloodstream to the insect life cycle stage in vitro. Moreover, mutant cells are characterised by a low mitochondrial transcript abundance. Together, these data establish that gBP21 contributes a non-essential function to the RNA editing reaction and further suggest that the protein is involved in additional mitochondrial processes which impact a larger pool of mitochondrial transcripts.  (+info)

RNA determinants for translational editing. Mischarging a minihelix substrate by a tRNA synthetase. (5/1357)

The fidelity of protein synthesis requires efficient discrimination of amino acid substrates by aminoacyl-tRNA synthetases. Accurate discrimination of the structurally similar amino acids, valine and isoleucine, by isoleucyl-tRNA synthetase (IleRS) results, in part, from a hydrolytic editing reaction, which prevents misactivated valine from being stably joined to tRNAIle. The editing reaction is dependent on the presence of tRNAIle, which contains discrete D-loop nucleotides that are necessary to promote editing of misactivated valine. RNA minihelices comprised of just the acceptor-TPsiC helix of tRNAIle are substrates for specific aminoacylation by IleRS. These substrates lack the aforementioned D-loop nucleotides. Because minihelices contain determinants for aminoacylation, we thought that they might also play a role in editing that has not previously been recognized. Here we show that, in contrast to tRNAIle, minihelixIle is unable to trigger the hydrolysis of misactivated valine and, in fact, is mischarged with valine. In addition, mutations in minihelixIle that enhance or suppress charging with isoleucine do the same with valine. Thus, minihelixIle contains signals for charging (by IleRS) that are independent of the amino acid and, by itself, minihelixIle provides no determinants for editing. An RNA hairpin that mimics the D-stem/loop of tRNAIle is also unable to induce the hydrolysis of misactivated valine, both by itself and in combination with minihelixIle. Thus, the native tertiary fold of tRNAIle is required to promote efficient editing. Considering that the minihelix is thought to be the more ancestral part of the tRNA structure, these results are consistent with the idea that, during the development of the genetic code, RNA determinants for editing were added after the establishment of an aminoacylation system.  (+info)

RNA editing of the human serotonin 5-hydroxytryptamine 2C receptor silences constitutive activity. (6/1357)

RNA transcripts encoding the serotonin 5-hydroxytryptamine 2C (5-HT2C) receptor (5-HT2CR) undergo adenosine-to-inosine RNA editing events at up to five specific sites. Compared with rat brain, human brain samples expressed higher levels of RNA transcripts encoding the amino acids valine-serine-valine (5-HT2C-VSV) and valine-glycine-valine (5-HT2C-VGV) at positions 156, 158, and 160, respectively. Agonist stimulation of the nonedited human receptor (5-HT2C-INI) and the edited 5-HT2C-VSV and 5-HT2C-VGV receptor variants stably expressed in NIH-3T3 fibroblasts demonstrated that serotonergic agonists were less potent at the edited receptors. Competition binding experiments revealed a guanine nucleotide-sensitive serotonin high affinity state only for the 5-HT2C-INI receptor; the loss of high affinity agonist binding to the edited receptor demonstrates that RNA editing generates unique 5-HT2CRs that couple less efficiently to G proteins. This reduced G protein coupling for the edited isoforms is primarily due to silencing of the constitutive activity of the nonedited 5-HT2CR. The distinctions in agonist potency and constitutive activity suggest that different edited 5-HT2CRs exhibit distinct responses to serotonergic ligands and further imply that RNA editing represents a novel mechanism for controlling physiological signaling at serotonergic synapses.  (+info)

Mutational analysis of apolipoprotein B mRNA editing enzyme (APOBEC1). structure-function relationships of RNA editing and dimerization. (7/1357)

APOBEC1 is the catalytic subunit of an enzyme complex that mediates apolipoprotein (apo) B mRNA editing. It dimerizes in vitro and requires complementation factor(s) for its editing activity. We have performed a systematic analysis of the structure-functional relationship of APOBEC1 by targeted mutagenesis of various sequence motifs within the protein. Using in vitro RNA editing assay, we found that basic amino acid clusters at the amino-terminal region R15R16R17 and R33K34, are essential for apoB mRNA editing. Mutation of R15R16R17 to K15K16K17 and mutation of R33K34 simultaneously to A33A34 almost completely abolished in vitro editing activity. The carboxy-terminal region of APOBEC1 contains a leucine-rich motif. Deletion analysis of this region indicates that residues 181 to 210 are important for in vitro apoB mRNA editing. Single amino acid substitutions demonstrate that L182, I185, and L189 are important residues required for normal editing function. Furthermore, the double mutant P190A/P191A also lost >90% of editing activity which suggests that a beta turn in this region of the molecule may be essential for proper functioning of APOBEC1. It was suggested that dimerization of APOBEC1 creates an active structure for deamination of apoB mRNA. When we examined the dimerization potential of truncated APOBEC1s using both amino and carboxy termini deletion mutants, we found that amino-terminal deletions up to residue A117 did not impair dimerization activity whereas carboxy-terminal deletions showed diminished dimerization. The systematic and extensive mutagenesis experiments in this study provide information on the role of various sequence motifs identified in APOBEC1 in enzyme catalysis and dimerization.  (+info)

The reversible change of GluR2 RNA editing in gerbil hippocampus in course of ischemic tolerance. (8/1357)

The ischemic tolerance is known to show protective effects on the neurons and the restricted Ca2+ influx through Ca2+ channels might be involved. In alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor, ribonucleic acid (RNA) editing of the GluR2 subunit determines receptor desensitization and Ca2+ permeability. The authors investigated the effect of ischemic tolerance on the messenger RNA editing of Q/R and R/G sites of GluR2 subunit in hippocampus. It was found that the rate of RNA editing in Q/R site showed no change (100% edited), whereas that in R/G site decreased significantly (83.3% normal editing level to 60.4%) at day 3 (preconditioning period) and returned to normal level at day 14 (after preconditioning period). Further investigation revealed that the decrease of editing rate in ischemic tolerance resulted mainly from the decrease of editing in CA1 area.  (+info)

论文信息:Zhuyun Bian, Yajia Ni, Jin-Rong Xu, Huiquan Liu*.A-to-I mRNA editing in fungi: occurrence, function, and evolution. Cellular and Molecular Life Sciences (2019) 76:329-340.. JCR分区Q1,中科院大类分区二区,IF=6.721. 论文摘要: A-to-I RNA editing is an important post-transcriptional modification that converts adenosine (A) to inosine (I) in RNA molecules via hydrolytic deamination. Although editing of mRNAs catalyzed by adenosine deaminases acting on RNA (ADARs) is an evolutionarily conserved mechanism in metazoans, organisms outside the animal kingdom lacking ADAR orthologs were thought to lack A-to-I mRNA editing. However, recent discoveries of genome-wide A-to-I mRNA editing during the sexual stage of the wheat scab fungus Fusarium graminearum, model filamentous fungus Neurospora crassa, Sordaria macrospora, and an early diverging filamentous ascomycete Pyronema confluens indicated that A-to-I mRNA editing is likely an evolutionarily conserved feature in ...
High-throughput sequencing (HTS) provides a powerful solution for the genome-wide identification of RNA-editing sites. However, it remains a great challenge to distinguish RNA-editing sites from genetic variants and technical artifacts caused by sequencing or read-mapping errors. Here we present RES-Scanner, a flexible and efficient software package that detects and annotates RNA-editing sites using matching RNA-seq and DNA-seq data from the same individuals or samples. RES-Scanner allows the use of both raw HTS reads and pre-aligned reads in BAM format as inputs. When inputs are HTS reads, RES-Scanner can invoke the BWA mapper to align reads to the reference genome automatically. To rigorously identify potential false positives resulting from genetic variants, we have equipped RES-Scanner with sophisticated statistical models to infer the reliability of homozygous genotypes called from DNA-seq data. These models are applicable to samples from either single individuals or a pool of multiple individuals
The complete nucleotide sequence of the P gene of simian virus 41 (SV41) was determined. The gene was found to be 1406 nucleotides long and to contain a relatively small open reading frame encoding a cysteine-rich V protein with a calculated M r of 24076. We have demonstrated that RNA-editing events occur in SV41 P gene transcripts and that the ratio of edited mRNAs to faithfully copied mRNA (P-mRNA: V-mRNA) is about 1:5 at either 24 or 40 h post-infection. The mRNA with two G insertions was capable of encoding a P protein of 395 amino acids with a predicted M r of 41992. A kinetic study of P and V proteins by Western blot analysis showed that in virus-infected cells the amounts of both proteins were almost equal although the V-mRNA was considerably more abundant than the P-mRNA. Alignment of the SV41 P and V proteins with those of nine other paramyxoviruses demonstrated that irregular gaps were present around the RNA-editing sites.
A tripartite motif located in the centre of the 7.5kb exon 26 of apolipoprotein B (apoB) mRNA directs editosome assembly and site-specific cytidine-to-uridine editing at nucleotide 6666. apoB mRNA editing is a post-transcriptional event, occurring primarily at the time exon 26 is spliced or at a time after splicing, but before nuclear export. We show, through reporter RNA constructs, that RNA splice sites suppress editing of precursor RNAs when placed proximal or distal to the editing site. Processed RNAs were edited more efficiently than precursor RNAs. Mutation of both the splice donor and acceptor sites was necessary for RNAs to be edited efficiently. The results suggested that commitment of pre-mRNA to the splicing and/or nuclear-export pathways may play a role in regulating editing-site utilization. The HIV-1 Rev-Rev response element (RRE) interaction was utilized to uncouple the commitment of precursor RNAs to the spliceosome assembly pathway and associated nuclear-export pathway. Under ...
Ocean Acoustic Tomography requires deep-ocean moorings whose horizontal excursions are either small or accurately measured. The present study rigorously investigates the former case: the design of stiff moorings to meet any particular horizontal excursion goal (e.g., 25 meters) under two typical ocean current-versus-depth profiles. Moorings are considered for tomographic transmitters and receivers at depths ranging from one thousand to four thousand meters. Mooring components considered include steel sphere, glass ball, and syntactic foam buoyancy; jacketed 3 x 19 wire and electromagnetic cable; and a realistic (large) battery pack for the acoustic transmitter. Kevlar mooring line was considered and rejected. The basic tool of this study is a well-verified computer program that simulates mooring motion. Many runs of this program have yielded enough data to make plots showing mooring cost as a function of excursion, depth, and mooring type. It has been found that cost and excursion are very sensitive to
Definition of substitutional in the Financial Dictionary - by Free online English dictionary and encyclopedia. What is substitutional? Meaning of substitutional as a finance term. What does substitutional mean in finance?
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antibody-antibodies.com is the marketplace for research antibodies. Find the right antibody for your research needs. Mechanism of U insertion RNA editing in trypanosome mitochondria: the bimodal TUTase activity of the core complex.
Line number RuleID ViolationType Message Line #------------ #------------ # Validation for #430725 annotations in 430768 lines #------------ #Line number RuleID ViolationType Message Line #------------ # GO_AR:0000014 Valid GO term ID Error count: 212 3146 GO_AR:0000014 Error The relation has_direct_input in the c16 annotation extension is an obsolete relation MGI MGI:1917115 A1cf GO:0016556 MGI:MGI:4943819,PMID:20541607 IGI MGI:MGI:104663 P APOBEC1 complementation factor 1810073H04Rik,ACF,apobec-1 complementation factor protein taxon:10090 20140709 MGI has_direct_input(MGI:MGI:88052),occurs_in(EMAPA:16900) 9354 GO_AR:0000014 Error The relation has_direct_input in the c16 annotation extension is an obsolete relation MGI MGI:105377 Adam19 GO:0006509 MGI:MGI:3625788,PMID:11116142 IMP P a disintegrin and metallopeptidase domain 19 (meltrin beta) Mltnb protein taxon:10090 20150513 MGI ...
we used RNA-Seq to quantify the RNA editing level at more than 8,000 previously annotated exonic A-to-I RNA editing sites in two brain regions - prefrontal cortex and cerebellum - of humans, chimpanzees and rhesus macaques. We observed substantial conservation of RNA editing levels between the brain regions, as well as among the three primate species. Evolutionary changes in RNA editing were nonetheless evident among the species. Across lifespan, we observed an increase of the RNA editing level with advanced age in both brain regions of all three primate species.
Sigma-Aldrich offers abstracts and full-text articles by [Zhenqiu Huang, Drahomíra Faktorová, Adéla Křížová, Lucie Kafková, Laurie K Read, Julius Lukeš, Hassan Hashimi].
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Both miRNAs and A-to-I RNA editing, a widespread nucleotide modification mechanism, have recently emerged as key players in cancer pathophysiology. However, the functional impact of RNA editing of miRNAs in cancer remains largely unexplored. Here, we focused on an ADAR2-catalyzed RNA editing site within the miR-379-5p seed region. This site was under-edited in tumors relative to normal tissues, with a high editing level being correlated with better patient survival times across cancer types. We demonstrated that in contrast to wild-type miRNA, edited miR-379-5p inhibited cell proliferation and promoted apoptosis in diverse tumor contexts in vitro, which was due to the ability of edited but not wild-type miR-379-5p to target CD97. Importantly, through nanoliposomal delivery, edited miR-379-5p mimics significantly inhibited tumor growth and extended survival of mice. Our study indicates a role of RNA editing in diversifying miRNA function during cancer progression and highlights the translational ...
Both miRNAs and A-to-I RNA editing, a widespread nucleotide modification mechanism, have recently emerged as key players in cancer pathophysiology. However, the functional impact of RNA editing of miRNAs in cancer remains largely unexplored. Here, we focused on an ADAR2-catalyzed RNA editing site within the miR-379-5p seed region. This site was under-edited in tumors relative to normal tissues, with a high editing level being correlated with better patient survival times across cancer types. We demonstrated that in contrast to wild-type miRNA, edited miR-379-5p inhibited cell proliferation and promoted apoptosis in diverse tumor contexts in vitro, which was due to the ability of edited but not wild-type miR-379-5p to target CD97. Importantly, through nanoliposomal delivery, edited miR-379-5p mimics significantly inhibited tumor growth and extended survival of mice. Our study indicates a role of RNA editing in diversifying miRNA function during cancer progression and highlights the translational ...
This annual meeting is one of a series seeking to improve and where possible standardise QA and QC across the Moorings sub-facilities through common techniques, procedures and tools.
/PRNewswire/ -- Research and Markets has announced the addition of the Global Mooring Systems Market Analysis & Trends - Industry Forecast to 2025 report to...
Plasmid pUC119-gRNA from Dr. Jen Sheens lab contains the insert guide RNA targeting AtPDS3 and is published in Nat Biotechnol. 2013 Aug;31(8):688-91. doi: 10.1038/nbt.2654. This plasmid is available through Addgene.
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Double-stranded RNA-specific adenosine deaminase is an enzyme that in humans is encoded by the ADAR gene (which stands for adenosine deaminase acting on RNA). Adenosine deaminases acting on RNA (ADAR) are enzymes responsible for binding to double stranded RNA (dsRNA) and converting adenosine (A) to inosine (I) by deamination. ADAR protein is a RNA-binding protein, which functions in RNA-editing through post-transcriptional modification of mRNA transcripts by changing the nucleotide content of the RNA. The conversion from A to I in the RNA disrupt the normal A:U pairing which makes the RNA unstable. Inosine is structurally similar to that of guanine (G) which leads to I to cytosine (C) binding. In RNA I functions the same as G in both translation and replication. Codon changes can arise from editing which may lead to changes in the coding sequences for proteins and their functions. Most editing site are found in noncoding regions of RNA such as untranslated regions (UTRs), Alu elements and long ...
A-to-I RNA-editing mediated by ADAR (adenosine deaminase acting on RNA) enzymes that converts adenosine to inosine in RNA sequence can generate mutations and alter gene regulation in metazoans. Previous studies have shown that A-to-I RNA-editing plays vital roles in mouse embryogenesis. However, the RNA-editing activities in early human embryonic development have not been investigated. Here, we characterized genome-wide A-to-I RNA-editing activities during human early embryogenesis by profiling 68 single cells from 29 human embryos spanning from oocyte to morula stages. We demonstrate dynamic changes in genome-wide RNA-editing during early human embryogenesis in a stage-specific fashion. In parallel with ADAR expression level changes, the genome-wide A-to-I RNA-editing levels in cells remained relatively stable until 4-cell stage, but dramatically decreased at 8-cell stage, continually decreased at morula stage. We detected 37 non-synonymously RNA-edited genes, of which 5 were frequently found in cells
RNA editing by deamination of adenosine to inosine is an evolutionarily conserved process involved in many cellular pathways, from alternative splicing to miRNA targeting. In humans, it is carried out by no less than three major adenosine deaminases acting on RNA (ADARs): ADAR1-p150, ADAR1-p110, and ADAR2. However, the first two derive from alternative splicing, so that it is currently impossible to delete ADAR1-p110 without also knocking out ADAR1-p150 expression. Furthermore, the expression levels of ADARs varies wildly among cell types, and no study has systematically explored the effect of each of these isoforms on the cell transcriptome. In this study, RNA immunoprecipitation (RIP)-sequencing on overexpressed ADAR isoforms tagged with green fluorescent protein (GFP) shows that each ADAR is associated with a specific set of differentially expressed genes, and that they each bind to distinct set of RNA targets. Our results show a good overlap with known edited transcripts, establishing RIP-seq as a
Background: Adenosine deaminases acting on RNA deaminate adenosines to inosines in structured regions of RNAs. The RNA-editing process occurs in millions of sites in the human transcriptome. As inosines are interpreted as guanosines during translation, this RNA-editing process can alter codons and therefore lead to the formation of proteins that are not encoded in the genome. A prominent adenosine to inosine deamination event is found in the mRNA encoding filamin A, an abundant actin crosslinking protein that links the cellular cortex and transmembrane proteins with the cytoskeleton. Changes in the editing pattern of the filamin A mRNA lead to the expression of altered filamin A which causes high blood pressure but also causes gastrointestinal inflammatory disorders. To understand the molecular consequences of the editing-induced amino acid exchange, the affected domain will be studied by structural and biophysical means.. Thesis description: We are looking for a highly motivated and dedicated ...
TY - JOUR. T1 - ADAR2 regulates RNA stability by modifying access of decay-promoting RNA-binding proteins. AU - Anantharaman, Aparna. AU - Tripathi, Vidisha. AU - Khan, Abid. AU - Yoon, Je Hyun. AU - Singh, Deepak K.. AU - Gholamalamdari, Omid. AU - Guang, Shuomeng. AU - Ohlson, Johan. AU - Wahlstedt, Helene. AU - Öhman, Marie. AU - Jantsch, Michael F.. AU - Conrad, Nicholas K.. AU - Ma, Jian. AU - Gorospe, Myriam. AU - Prasanth, Supriya G.. AU - Prasanth, Kannanganattu V.. PY - 2017/4/20. Y1 - 2017/4/20. N2 - Adenosine deaminases acting on RNA (ADARs) catalyze the editing of adenosine residues to inosine (A-to-I) within RNA sequences, mostly in the introns and UTRs (un-translated regions). The significance of editing within non-coding regions of RNA is poorly understood. Here, we demonstrate that association of ADAR2 with RNA stabilizes a subset of transcripts. ADAR2 interacts with and edits the 3Î.,UTR of nuclear-retained Cat2 transcribed nuclear RNA (Ctn RNA). In absence of ADAR2, the ...
A growing number of studies have focused on investigating circRNAs as crucial regulators in the progression of multiple cancer types. Nevertheless, the biological effects and underlying mechanisms of circRNAs in pancreatic ductal adenocarcinoma (PDAC) remain unclear. Differentially expressed circRNAs between cancerous tissue and adjacent normal tissues were identified by RNA sequencing in PDAC. Subsequently, in vitro and in vivo functional experiments were performed to investigate the functional roles of circNEIL3 in PDAC tumour growth and metastasis. Furthermore, RNA pull-down, dual-luciferase reporter assays, RNA immunoprecipitation (RIP) assays, fluorescent in situ hybridization (FISH) and Sanger sequencing assays were performed to examine the circular interaction among circNEIL3, miR-432-5p and adenosine deaminases acting on RNA 1 (ADAR1). CircNEIL3 was upregulated in PDAC and promoted the progression of PDAC cells both in vitro and in vivo. Mechanistically, circNEIL3 was shown to regulate the
Background: Adenosine deaminase acting on RNA-2 (ADAR2) enzyme catalyzes adenosine-to-inosine (A-to-I) RNA editing of mRNAs and microRNAs and controls brain development. However, the role of endothelial cell ADAR2 in vascular biology and inflammation has not been described so far.. Methods and Results: ADAR2 is expressed in human and murine endothelial cells and is 2-fold induced by hypoxia or hind limb ischemia in mice (P,0.05 for all). ADAR2 deficiency resulted in 73±12% impairment of leukocyte infiltration, in 53±4% reduced neovascularization, and a 40±6% decreased blood-flow recovery of ischemic muscle tissues in a hindlimb ischemia mouse model (P,0.001 for all). Mechanistically, among the highly ADAR2-regulated transcripts was interleukin-6 signal transducer (IL6ST or gp130), the receptor of interleukin-6 (IL-6). Silencing of ADAR2 resulted in a downregulation of gp130 mRNA and protein expression in endothelial cells by 65±5% and 50±5%, respectively (P,0.001 for both). Similarly, the ...
Abstract: RNA editing by the adenosine deaminase acting on RNA (ADAR) enzymes has been associated with many human neurological diseases including: epilepsy; suicidal depression; autism; pediatric glioblastoma; and ALS (Lou Gehrigs disease). RNA editing is ubiquitous in the animal kingdom. ADAR deaminates the RNA base adenosine (A) to inosine (I) in dsRNA molecules. Inosine is recognized by all cellular machineries as guanosine (G). ADAR specifically edits, recodes, a small number of adenosines in messenger RNA (mRNA) to such Gs. However, hyper editing acts more generally on perfect or nearly perfect double-stranded RNA (dsRNA). Within long dsRNA (,30bp), over 40% of adenosine residues are modified on both strands, generating numerous I-U mismatch pairs, and structurally destabilizing dsRNA. Dicer is an enzyme that cleaves near perfect long dsRNAs, and thus competes with ADAR. As a consequence, ADARs hyper editing has downstream consequences on Dicer products including gene expression ...
The posttranscriptional modification of messenger RNA precursors (pre-mRNAs) by base deamination can profoundly alter the physiological function of the encoded proteins. The recent identification of tRNA-specific adenosine deaminases (ADATs) has led to the suggestion that these enzymes, as well as the cytidine and adenosine deaminases acting on pre-mRNAs (CDARs and ADARs), belong to a superfamily of RNA-dependent deaminases. This superfamily might have evolved from an ancient cytidine deaminase. This article reviews the reactions catalysed by these enzymes and discusses their evolutionary relationships.. ...
Both TAR DNA binding protein of 43kDa (TDP-43) pathology and failure of RNA editing at the glutamine/arginine (Q/R) site of GluA2, a subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor, are the characteristic etiology-linked molecular abnormalities that concomitantly occur in the motor neurons of the majority of patients with amyotrophic lateral sclerosis (ALS), the most common adult-onset fatal motor neuron disease. Adenosine deaminase acting on RNA 2 (ADAR2) specifically catalyzes RNA editing at the Q/R site of GluA2, and conditional ADAR2 knockout mice (ADAR2flox/flox/VAChT-Cre.Fast ; AR2 mice) exhibit a progressive ALS phenotype with TDP-43 pathology-like TDP-43 mislocalization in the ADAR2-lacking motor neurons. Because Ca2+-permeable AMPA receptor-mediated mechanism underlies death of motor neurons in the AR2 mice, amelioration of exaggerated Ca2+ influx by AMPA receptor antagonists may be a potential ALS therapy. Here we showed that oral perampanel, a selective
The molecular drivers of human progenitor reprogramming into self-renewing leukemia stem cells (LSC) has remained elusive. Although DNA sequencing has uncovered gene mutations that promote abnormal RNA processing and leukemic transformation, gene product diversity also may be generated by RNA editing mediated by adenosine deaminase acting on RNA (ADAR) enzymes that regulate stem cell maintenance. In this study, RNA-sequencing studies reveal high levels of expression of inflammatory mediators in human blast crisis CML progenitors and in BCR-ABL transduced normal cord blood stem cells. Moreover, expression of the inflammation-responsive form of ADAR1 (p150) correlated with generation of an abnormally spliced GSK3β gene product that has been previously linked to LSC self-renewal. Together, we have demonstrated that ADAR1 drives hematopoietic cell fate by skewing cell differentiation - a trend which occurs during normal bone marrow aging - and promotes LSC self-renewal through alternative splicing ...
8-Azaadenosine is a potent ADAR1 (adenosine deaminases acting on double-stranded RNA) inhibitor. 8-Azaadenosine reduces A-to-I editing activity in a leukemia cell line, restores let-7 and inhibits leukemia stem cells self-renewal in vitro. - Mechanism of Action & Protocol.
BACKGROUND: Adenosine-to-inosine (A-to-I) editing is a site-selective post-transcriptional alteration of double-stranded RNA by ADAR deaminases that is crucial for homeostasis and development. Recently the Mouse Genomes Project generated genome sequences for 17 laboratory mouse strains and rich catalogues of variants. We also generated RNA-seq data from whole brain RNA from 15 of the sequenced strains. RESULTS: Here we present a computational approach that takes an initial set of transcriptome/genome mismatch sites and filters these calls taking into account systematic biases in alignment, single nucleotide variant calling, and sequencing depth to identify RNA editing sites with high accuracy. We applied this approach to our panel of mouse strain transcriptomes identifying 7,389 editing sites with an estimated false-discovery rate of between 2.9 and 10.5%. The overwhelming majority of these edits were of the A-to-I type, with less than 2.4% not of this class, and only three of these edits could not be
BACKGROUND: Adenosine-to-inosine (A-to-I) editing is a site-selective post-transcriptional alteration of double-stranded RNA by ADAR deaminases that is crucial for homeostasis and development. Recently the Mouse Genomes Project generated genome sequences for 17 laboratory mouse strains and rich catalogues of variants. We also generated RNA-seq data from whole brain RNA from 15 of the sequenced strains. RESULTS: Here we present a computational approach that takes an initial set of transcriptome/genome mismatch sites and filters these calls taking into account systematic biases in alignment, single nucleotide variant calling, and sequencing depth to identify RNA editing sites with high accuracy. We applied this approach to our panel of mouse strain transcriptomes identifying 7,389 editing sites with an estimated false-discovery rate of between 2.9 and 10.5%. The overwhelming majority of these edits were of the A-to-I type, with less than 2.4% not of this class, and only three of these edits could not be
Array ( [0] => 30 [1] => 31 [2] => 32 [3] => 34 [4] => 33 [5] => 49 ) Array ( [1513164984] => Array ( [timeid] => 1513164984 [id] => 14978 [title] => Applications of stimuli-responsive nanoscale drug delivery systems in translational research. (Drug Discov Today, Nov 2017) [time] => 13 December 2017 11:36:24 [postcat] => 30 ) [1511955285] => Array ( [timeid] => 1511955285 [id] => 14880 [title] => CSI Deputy Director, Prof Chng Wee Joo, Appointed Provosts Chair at NUSMed [time] => 29 November 2017 11:34:45 [postcat] => 31 ) [1511286152] => Array ( [timeid] => 1511286152 [id] => 14843 [title] => Triple negative breast cancer in Asia: An insiders view. (Cancer Treat Rev, Nov 2017) [time] => 21 November 2017 17:42:32 [postcat] => 30 ) [1510763331] => Array ( [timeid] => 1510763331 [id] => 14808 [title] => CSI Research Scientist Awarded the ASH Abstract Achievement Award! [time] => 15 November 2017 16:28:51 [postcat] => 31 ) [1510588491] => Array ( [timeid] => 1510588491 [id] => 14803 [title] => ...
Abstract: Mitochondrial mRNAs in kinetoplastids require extensive U-insertion/deletion editing that progresses 3-to-5 in small blocks, each directed by a guide RNA (gRNA), and exhibits substrate and developmental stage-specificity by unsolved mechanisms. Here, we address compositionally related factors, collectively known as the mitochondrial RNA-binding complex 1 (MRB1) or gRNA-binding complex (GRBC), that contain gRNA, have a dynamic protein composition, and transiently associate with several mitochondrial factors including RNA editing core complexes (RECC) and ribosomes. MRB1 controls editing by still unknown mechanisms. We performed the first next-generation sequencing study of native subcomplexes of MRB1, immunoselected via either RNA helicase 2 (REH2), that binds RNA and associates with unwinding activity, or MRB3010, that affects an early editing step. The particles contain either REH2 or MRB3010 but share the core GAP1 and other proteins detected by RNA photo-crosslinking. Analyses of ...
TY - JOUR. T1 - Elucidation of the RNA Recognition Code for Pentatricopeptide Repeat Proteins Involved in Organelle RNA Editing in Plants. AU - Yagi, Yusuke. AU - Hayashi, Shimpei. AU - Kobayashi, Keiko. AU - Hirayama, Takashi. AU - Nakamura, Takahiro. N1 - Copyright: Copyright 2013 Elsevier B.V., All rights reserved.. PY - 2013/3/5. Y1 - 2013/3/5. N2 - Pentatricopeptide repeat (PPR) proteins are eukaryotic RNA-binding proteins that are commonly found in plants. Organelle transcript processing and stability are mediated by PPR proteins in a gene-specific manner through recognition by tandem arrays of degenerate 35-amino-acid repeating units, the PPR motifs. However, the sequence-specific RNA recognition mechanism of the PPR protein remains largely unknown. Here, we show the principle underlying RNA recognition for PPR proteins involved in RNA editing. The distance between the PPR-RNA alignment and the editable C was shown to be conserved. Amino acid variation at 3 particular positions within the ...
Background The post-transcriptional processing of pre-mRNAs by RNA editing contributes significantly to the complexity of the mammalian transcriptome. RNA editing by site-selective A-to-I modification also regulates protein function through recoding of genomically specified sequences. The adenosine deaminase ADAR2 is the main enzyme responsible for recoding editing and loss of ADAR2 function in mice leads to a phenotype of epilepsy and premature death. Although A-to-I RNA editing is known to be subject to developmental and cell-type specific regulation, there is little knowledge regarding the mechanisms that regulate RNA editing in vivo. Therefore, the characterization of ADAR expression and identification of alternative ADAR variants is an important prerequisite for understanding the mechanisms for regulation of RNA editing and the causes for deregulation in disease. Methodology/Principal Findings Here we present evidence for a new ADAR2 splice variant that extends the open reading frame of ADAR2 by
abstract = {Adenosine-to-inosine (A-to-I) RNA editing is a conserved post-transcriptional mechanism mediated by ADAR enzymes that diversifies the transcriptome by altering selected nucleotides in RNA molecules1. Although many editing sites have recently been discovered2,3,4,5,6,7, the extent to which most sites are edited and how the editing is regulated in different biological contexts are not fully understood8,9,10. Here we report dynamic spatiotemporal patterns and new regulators of RNA editing, discovered through an extensive profiling of A-to-I RNA editing in 8,551 human samples (representing 53 body sites from 552 individuals) from the Genotype-Tissue Expression (GTEx) project and in hundreds of other primate and mouse samples. We show that editing levels in non-repetitive coding regions vary more between tissues than editing levels in repetitive regions. Globally, ADAR1 is the primary editor of repetitive sites and ADAR2 is the primary editor of non-repetitive coding sites, whereas the ...
Double-stranded RNA adenosine deaminase (ADAR1) is an ubiquitous enzyme in metazoa that edits pre-mRNA changing adenosine to inosine in regions of double-stranded RNA. Zalpha, an N-terminal domain of human ADAR1 encompassing 76 amino acid residues, shows apparent specificity for the left-handed Z-DN …
Source: NIH.gov. A set of proteins involved in the bodys natural defences produces a large number of mutations in human DNA, according to a study led by researchers at the National Institutes of Health. The findings suggest that these naturally produced mutations are just as powerful as known cancer-causing agents in producing tumors.. The proteins are part of a group called apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) cytidine deaminases. The investigators found that APOBEC mutations can outnumber all other mutations in some cancers, accounting for over two-thirds in some bladder, cervical, breast, head and neck, and lung tumours.. The scientists published their findings online July 14 in the journal Nature Genetics. Dmitry Gordenin, Ph.D., is corresponding author of the paper and a senior associate scientist at the National Institute of Environmental Health Sciences (NIEHS), part of NIH. He said scientists knew the main functions of APOBEC cytosine deaminases were ...
Has A-to-I RNA editing activity on extended dsRNA: edits RNA-binding protein Rnp4F. A-to-I editing of pre-mRNAs acts predominantly through nervous system targets to affect adult nervous system integrity, function and behavior. Essential for adaptation to environmental stresses, such as oxygen deprivation, and for the prevention of premature neuronal degeneration, through the editing of ion channels as targets.
To investigate whether the JAK-STAT (Janus kinase-signal transducers and activators of transcription) pathway participates in the regulation of APOBEC3G (Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G) gene transcription and to study the molecular mechanisms of interferon resistance in patients with chronic hepatitis B (CHB), changes in APOBEC3G and STAT-1 expression levels in HepG2.2.15 cells after treatment with various concentrations of IFN-a, were detected using real-time RT-PCR and Western-blot. In addition, the differences in STAT-1 and APOBEC3G expression in liver tissues were also observed in patients with different anti-viral responses to IFN-a. It is found that IFN-a suppressed HBV replication and expression markedly in HepG2.2.15 cells, and simultaneously enhanced APOBEC3G expression in a dose- or time-dependent manner within a certain range. Moreover, a corresponding gradual increase in STAT-1 expression levels was also observed. The expression levels of STAT-1 and
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the double-stranded RNA adenosine deaminase family of RNA-editing enzymes and may play a regulatory role in RNA editing. [provided by RefSeq, Jul 2008 ...
The most significant finding of this study is that the expression and activity of the RNA editase ADAR1 is upregulated in lungs subjected to endotoxin-induced microvascular injury and in alveolar macrophages stimulated with endotoxin, live bacteria, or IFN. These findings implicate for the first time RNA editing as a possible inflammatory event. Specifically, the data suggest that A-to-I RNA editing is involved in the pathogenic mechanisms that lead to acute lung injury. Another significant finding is that ADAR1 is expressed in sham mouse lungs, which was previously demonstrated only in the rat.8 The sequence of early production of IFN, a known inducer of ADAR1,12 followed by ADAR1 expression and development of microvascular lung injury, suggests that A-to-I RNA editing may be a proximal event in the inflammatory cascade involved in the pathogenesis of microvascular lung injury. Furthermore, it is conceivable that early induction of pulmonary IFN during the inflammatory process could be the ...
RNA editing is a regulatory mechanism in which nucleotides are altered posttranscriptionally and most frequently involves conversion of adenosine to inosine, which is recognized as a guanosine during translation. Chen and colleagues performed RNA sequencing analysis to identify molecular changes in hepatocellular carcinoma (HCC) samples that might contribute to disease progression, and they detected elevated adenosine-to-inosine RNA editing of antizyme inhibitor 1 (AZIN1) in HCC samples compared with adjacent normal tissues. The frequency of AZIN1 editing increased during HCC progression and was correlated with liver cirrhosis, tumor recurrence, and poor prognosis, suggesting that this recoding event may promote HCC pathogenesis. AZIN1 RNA modification was mediated by the p110 isoform of adenosine deaminase, RNA-specific (ADAR1), but not by other ADAR family members, and resulted in substitution of glycine for serine at residue 367 in the AZIN1 protein, which was predicted to induce a ...
The current research, which involved 13 patients with lupus and eight healthy participants, was based on Laxminarayanas earlier findings that 150-kDa ADAR1, one of the three enzymes involved in editing gene messages, is higher in the T cells of lupus patients compared to those without lupus. ADARs are ademosine deaminases that act on RNA.. Laxminarayana made the initial finding about 150-kDa ADAR1 levels in 2002 and has been working to solve the mystery of how it is related to the development of lupus. In the current study, Laxminarayana found that the higher levels of 150-kDa ADAR1 alters the editing induced by two other ADAR enzymes and may cause an imbalance of proteins. Editing by the two other ADAR enzymes is a normal cellular process; it is 150-kDa ADAR1 that causes normal editing to go awry.. The process is complicated and took Laxminarayana years to uncover. The current studies demonstrate that, essentially, too much 150-kDa ADAR1 results in an increase in the gene message of ...
While most discussions about big data typically focus on the massive size of data, a better discussion might be about what big data is really providing: objective information about peoples behavior - uncensored, unfiltered, unedited. This Harvard Business Review paper, Predicting Customers (Unedited) Behavior explores how the analysis of big data is increasingly about finding the connections between peoples behavior and outcomes. ...
While most discussions about big data typically focus on the massive size of data, a better discussion might be about what big data is really providing: objective information about peoples behavior - uncensored, unfiltered, unedited. This Harvard Business Review paper, Predicting Customers (Unedited) Behavior explores how the analysis of big data is increasingly about finding the connections between peoples behavior and outcomes. ...
Spatial/temporal control of Cas9 guide RNA expression could considerably expand the utility of CRISPR-based technologies. Current approaches based on tRNA processing offer a promising strategy but suffer from high background. Here, to address this limitation, we present a screening platform which allows simultaneous measurements of the promoter strength, 5, and 3 processing efficiencies across a library of tRNA variants. This analysis reveals that the sequence determinants underlying these activities, while overlapping, are dissociable. Rational design based on the ensuing principles allowed us to engineer an improved tRNA scaffold that enables highly specific guide RNA production from a Pol-II promoter. When benchmarked against other reported systems this tRNA scaffold is superior to most alternatives, and is equivalent in function to an optimized version of the Csy4-based guide RNA release system. The results and methods described in this manuscript enable avenues of research both in genome
The moorings are in a well-sheltered anchorage.. Farmers Cay Yacht Club announced in January 2016 that its nine moorings in the Harbour have been redone with all new stainless steel chain and line.. Also, the dock has been re-planked and braced. The restaurant is open from 9 am to midnight.. Other moorings close to the Little Harbour are owned by other businesses on the Cay and it can be tricky to find out which one to pay as the mooring balls are poorly marked.. The tidal current is swift and the bottom well scoured, so unless your draft allows anchoring in the sand to the east of the channel, it is best to use a mooring.. See comments from cruisers at bottom of page re. condition of moorings.. Last updated July 2017.. Note that Guana Hideaways Marina on Great Guana Cay is not operational (February 2017) and has been removed from Noonsite listings.. ...
MOORING MASTER 08 June, 2021 tandem and CALM buoy mooring and loading of export tanker Reporting to: OIM NOTE: The responsibilities include the main Gener...
This gene encodes a member of the AID/APOBEC family of polynucleotide (deoxy)cytidine deaminases, which convert cytidine to uridine. Other AID/APOBEC family members are involved in mRNA editing, somatic hypermutation and recombination of immunoglobulin genes, and innate immunity to retroviral infection. [provided by RefSeq, Jul 2008 ...
Bujnicki lab. Our group is involved in theoretical and experimental research on nucleic acids and proteins. The current focus is on RNA sequence-structure-function relationships (in particular 3D modeling), RNA-protein complexes, and enzymes acting on RNA.
Bujnicki lab. Our group is involved in theoretical and experimental research on nucleic acids and proteins. The current focus is on RNA sequence-structure-function relationships (in particular 3D modeling), RNA-protein complexes, and enzymes acting on RNA.
Current Research and Scholarly Interests The Li Lab is primarily interested in RNA editing mediated by ADAR enzymes. We co-discovered that the major function of RNA editing is to label endogenous dsRNAs as self to avoid being recognized as non-self by MDA5, a host innate immune dsRNA sensor, leading us to pursue therapeutic applications in cancer, autoimmune diseases, and viral infection. The other major direction of the lab is to develop technologies to harness endogenous ADAR enzymes for site-specific transcriptome engineering. ...
stability and fatigue of analysis mooring system and which software is better for solve it?Sorry i dont know dat but i wanna know the th emooring te...
Kegunaan tali mooring kapal memang sangat bermanfaat bagi semua pihak di areal dermaga. Tidak hanya akan mempermudah dalam segi penambat yang aman dan
CSA-dependent degradation of CSB by the ubiquitin-proteasome pathway establishes a link between complementation factors of the Cockayne syndrome ...
Upon binding with guide RNA, the two structural lobes of Cas9 reorient so that the two nucleic acid binding clefts face each other, forming a central DNA binding channel that interfaces with target DNA.
CRISPR-Cpf1 Bound to Target DNA and Guide RNA (U6M63VBSL) by caseysteffen on Shapeways. Learn more before you buy, or discover other cool products in Mathematical Art.
Happy Monday!!! Tomorrow is my birthday!!! WOoHoO- for those who care Ill be 25 years old. Go Me. Last week I had my query critique. It went better than I could ever expected. It has since then been revised and Ive tested the waters now. Thats right Ive dived into the querying world. And Ive been cupcaked (also known as rejected but those are hurtful and harsh words and arent used here. I was given the word my fabulous blogger friend Karen Amanda Hooper). Its not always a negative (its a cupcake for junk sake, cupcakes rock). When I received my first one I was actually excited. My husband and I celebrated. Its like a rite of passage. Something you have to do to realize youre one step closer to that agent. There is an agent out for you. YOUR work is good enough. Dont give up. Just take each rejection with a grain of salt. Appreciate each company for even bothering to take a look. They dont have too. They look at thousands. So the next time you get a cupcake look at it as a positive. ...
This is the non-edited Straight Out Of the Camera (SOOC) shot that I took on a dreary overcast day when Jocelyn was already getting sick. It took me, Jaina, and Jayces therapist to get her to smile even this 1/2 smile. The newly put up Christmas tree was totally blocking my light (what little light I had at 4 PM on an overcast day) from the window. I am hoping to salvage this picture in GIMP and make it match the other 11 monthly pictures so I can print them in a collage frame next month ...
Methods. int :: Int -, repr h IntSource. add :: repr h Int -, repr h Int -, repr h IntSource. z :: repr (a, h) aSource. s :: repr h a -, repr (any, h) aSource. lam :: repr (a, h) b -, repr h (a -, b)Source. app :: repr h (a -, b) -, repr h a -, repr h bSource ...
We demonstrate that by altering the length of Cas9-associated guide RNA (gRNA) we were able to control Cas9 nuclease activity and simultaneously perform genome editing and transcriptional regulation with a single Cas9 protein. We exploited these principles to engineer mammalian synthetic circuits wi …
carbon plates: R&G - CFK plate 350 x 150 x 0,8mm - R&G - Carbon fibre sheet 3mm ( 150 x 340 ) - R&G - Carbon fibre sheet 1,5mm ( 150 x 340 ) - R&G - CFK pla
Plasmid pSpCas9_BB_2A-GFP_MAPRE1-gRNA#2 from Dr. Torsten Wittmanns lab contains the insert MAPRE1 gRNA #1 (targets Exon 1) and is published in Nat Cell Biol. 2018 Jan 29. pii: 10.1038/s41556-017-0028-5. doi: 10.1038/s41556-017-0028-5. This plasmid is available through Addgene.
利用CRISPER系統編輯基因,為您提供基因敲除(CRISPER)或激活本底基因表達(CRISPERa)的文庫篩選工具Guide RNA,不同Guide RNA工具形式可支持瞬轉、穩轉包病毒體系,亦或提供慢病毒顆粒。從各類小基因家族到全基因組范圍,為您提供靈活、方便和高可信度的篩選結果。. 我們的優勢 ...
Unedited responses from APPAs survey on Grounds/Landscaping, conducted April 2020. Are there any special tactics/protocols that have been implemented by the…
RNA editing. Octopuses and other coleoid cephalopods are capable of greater RNA editing (which involves changes to the nucleic ... Coleoids rely mostly on ADAR enzymes for RNA editing, which requires large double-stranded RNA structures to flank to the ... High levels of RNA editing do not appear to be present in more basal cephalopods or other molluscs.[118][119] ... More than 60% of RNA transcripts for coleoid brains are recoded by editing, compared to less than 1% for a human or fruit fly. ...
Single-molecule RNA FISH[edit]. Single-molecule RNA FISH, also known as Stellaris® RNA FISH,[11] is a method of detecting and ... Preparation and hybridization process - RNA[edit]. Cells, circulating tumor cells (CTCs), or formalin-fixed paraffin-embedded ( ... doi:10.1261/rna.2701111. PMC 3096040. PMID 21518807.. *^ a b c Bernasconi, B.; Karamitopolou-Diamantiis, E.; Tornillo, L.; ... RNA Fluorescent In Situ Hybridization for the Simultaneous Detection of Immature and Mature Long Noncoding RNAs in Adherent ...
RNA-based tests[edit]. These are based on detecting a leukemic specific RNA sequence. Generally this is achieved through the ... Significance[edit]. Level of MRD is a guide to prognosis or relapse risk[edit]. In some cases, the level of MRD at a certain ... Testing by hospitals and other labs[edit]. Where done[edit]. MRD testing is not yet a routine test, nor is it carried out in ... Resources[edit]. General[edit]. *Minimal Residual Disease. Website. Modern MRD Detection Technologies. July 2013. ...
RNA transcripts[edit]. Sometimes a gene, after being turned on, transcribes a product that (directly or indirectly) maintains ... MicroRNAs[edit]. MicroRNAs (miRNAs) are members of non-coding RNAs that range in size from 17 to 25 nucleotides. miRNAs ... sRNAs[edit]. sRNAs are small (50-250 nucleotides), highly structured, non-coding RNA fragments found in bacteria. They control ... Psychology and psychiatry[edit]. Early life stress[edit]. In a groundbreaking 2003 report, Caspi and colleagues demonstrated ...
RNA sequencing[edit]. RNA sequencing was one of the earliest forms of nucleotide sequencing. The major landmark of RNA ... RNAP sequencing[edit]. This method is based on use of RNA polymerase (RNAP), which is attached to a polystyrene bead. One end ... Sample preparation[edit]. The success of any DNA sequencing protocol relies upon the DNA or RNA sample extraction and ... History[edit]. Discovery of DNA structure and function[edit]. Deoxyribonucleic acid (DNA) was first discovered and isolated by ...
Xist and Tsix RNAs[edit]. Main article: Xist. The X-inactive specific transcript (Xist) gene encodes a large non-coding RNA ... demonstrating that Xist RNA is coating only one of the X-chromosomes. RNA FISH signals from Xist RNA are shown in red color, ... Mechanism[edit]. Cycle of X chromosome activation[edit]. X-inactivation is part of the activation cycle of the X chromosome ... Like Xist, the Tsix gene encodes a large RNA which is not believed to encode a protein. The Tsix RNA is transcribed antisense ...
Virus-like RNA-based origin[edit]. Sex might also have been present even earlier, in the hypothesized RNA world that preceded ... Other explanations[edit]. Geodakyan's evolutionary theory of sex[edit]. Geodakyan suggested that sexual dimorphism provides a ... Exposure to conditions that cause RNA damage could have led to blockage of replication and death of these early RNA life forms ... References[edit]. *^ a b Letunic, I; Bork, P (2006). "Interactive Tree of Life". Retrieved 23 July 2011.. ...
Translation table 1[edit]. Standard RNA codon table[edit]. Amino-acid biochemical properties Nonpolar Polar Basic Acidic ↓ ... Inverse RNA codon table[edit]. Inverse table for the standard genetic code (compressed using IUPAC notation)[14] Amino acid. ... In RNA, it is replaced with uracil (U).[16] This is the only difference between the standard RNA codon table and the standard ... RNA codon involved Translation with this code Standard translation Notes Standard 1 Includes translation table 8 (plant ...
Micro-RNA[edit]. MicroRNA are small RNA fragments produced in the host cells thanks to a specific enzymatic mechanism. They ... References[edit]. *^ a b c "Viral Zone". ExPASy. Retrieved 15 June 2015.. ... Effect on host immunity[edit]. In the host, several mechanisms of the insect immune system can be triggered when the wasp lays ... Evolution[edit]. Nucleic acid analysis suggests a very long association of the viruses with the wasps (greater than 70 million ...
Spliceosomal complex[edit]. Introns[edit]. The word intron is derived from the terms intragenic region,[1] and intracistron,[2] ... RNA splicing, in molecular biology, is a form of RNA processing in which a newly made precursor messenger RNA (pre-mRNA) ... doi:10.1261/rna.1821809. PMC 2779669. PMID 19861426.. *^ a b Shkreta L, Chabot B (2015). "The RNA Splicing Response to DNA ... External links[edit]. *Virtual Cell Animation Collection: mRNA Splicing. *RNA+Splicing at the US National Library of Medicine ...
RNA and protein-based approaches[edit]. Metatranscriptomics studies have been performed to study the gene expression of ... Research methods[edit]. Targeted amplicon sequencing[edit]. Targeted amplicon sequencing relies on having some expectations ... References[edit]. *^ Lederberg, J; McCray, AT (2001). "'Ome Sweet 'Omics-a genealogical treasury of words". Scientist. 15: 8.. ... Plants[edit]. Light micrograph of a cross section of a coralloid root of a cycad, showing the layer that hosts symbiotic ...
RNA polymerase[edit]. The first polymerase enzyme isolated from T. aquaticus in 1974 was a DNA-dependent RNA polymerase,[8] ... References[edit]. *^ Thomas Brock's essay "Life at High Temperatures" *^ a b Brock TD & Freeze H (1969). "Thermus aquaticus, a ... Enzymes from T. aquaticus[edit]. T. aquaticus has become famous as a source of thermostable enzymes, particularly the Taq DNA ... Biology[edit]. T. aquaticus shows best growth at 65 to 70 °C (149 °F to 158 °F), but can survive at temperatures of 50 °C to 80 ...
RNA editing[edit]. The mRNA transcripts of the SDHB gene in human are edited through an unknown mechanism at ORF nucleotide ... "Hypoxia-inducible C-to-U coding RNA editing downregulates SDHB in monocytes". PeerJ. 1: e152. doi:10.7717/peerj.152. PMC ... "Hypoxia-inducible C-to-U coding RNA editing downregulates SDHB in monocytes". PeerJ. 1: e152. doi:10.7717/peerj.152. PMC ... References[edit]. *^ a b c GRCh38: Ensembl release 89: ENSG00000117118 - Ensembl, May 2017 ...
... in DNA and RNA studies[edit]. In studies like DNA fingerprinting the lysis buffer is used for DNA isolation. Dish ... Commonly used buffers[edit]. NP-40 lysis buffer[edit]. It may be the most widely used lysis buffer. The solubilizing agent is ... Additives[edit]. Salts[edit]. Lysis buffer usually contains one or more salts. The function of salts in lysis buffer is to ... Components[edit]. Buffer[edit]. Buffer creates an environment for isolated proteins. Each buffer choice has a specific pH range ...
RNA editing[edit]. The pre-mRNA of this protein is subject to RNA editing.[11] ... Type[edit]. A to I RNA editing is catalyzed by a family of adenosine deaminases acting on RNA (ADARs) that specifically ... GABRA3 - a channel subunit which undergoes similar RNA editing. References[edit]. *^ a b c GRCh38: Ensembl release 89: ... Consequences[edit]. Structure[edit]. Editing results in a codon (I/V) change from (ATT) to (GTT) resulting in translation of a ...
Defective interfering RNA[edit]. Defective interfering RNA (DI) molecules are RNAs that are produced from the viral genome but ... p22[edit]. The p22 protein is a movement protein that is required for the virus to spread from cell to cell. P22 is an RNA- ... Replication[edit]. A TBSV virion contains one copy of its positive-sense single-stranded RNA genome, which is linear and lacks ... Genome and protein complement[edit]. TBSV is a positive-sense single-stranded RNA virus with a linear genome of ~4800 ...
RNA[edit]. RNA interference is under study for possible use as a spray-on insecticide by multiple companies, including Monsanto ... The RNA could be modified to maintain its effectiveness as target species evolve tolerance to the original. RNA is a relatively ... Monsanto has invested in multiple companies for their RNA expertise, including Beeologics (for RNA that kills a parasitic mite ... External links[edit]. Wikimedia Commons has media related to Biopesticides.. *Bioinsecticides Market (Acquire Market Research) ...
DNA and RNA base pair complementarity[edit]. Complementarity between two antiparallel strands of DNA. The top strand goes from ... See also[edit]. *Base pair. References[edit]. *^ a b c d e f g h Watson, James, Cold Spring Harbor Laboratory, Tania A. Baker, ... Self-complementarity and hairpin loops[edit]. A sequence of RNA that has internal complementarity which results in it folding ... Bioinformatics[edit]. Complementarity allows information found in DNA or RNA to be stored in a single strand. The complementing ...
Small RNA[edit]. Bacterial small RNAs play important roles in many cellular processes; 11 small RNAs have been experimentally ... See also[edit]. *Anti-Q RNA. References[edit]. *^ .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output . ... Antibacterial resistance[edit]. Multi drug resistance[edit]. Main article: Vancomycin-resistant Enterococcus ... External links[edit]. Wikimedia Commons has media related to Enterococcus faecalis.. *Type strain of Enterococcus faecalis at ...
Ribosome-mediated attenuation[edit]. In this situation RNA polymerase is dependent on (lagging) ribosome activity; if the ... Lactis-leu-phe leader RNA motif Attenuation in eukaryotes[edit]. Research conducted on microRNA processing showed an evidence ... Classes of attenuators[edit]. Attenuators may be classified according to the type of molecule which induces the change in RNA ... RNA thermometers[edit]. Temperature dependent loop formations introduce temperature-dependence in the expression of downstream ...
RNA ligases[edit]. Of particular interest are DNA ligases.[5] These molecules have demonstrated remarkable chemoselectivity in ... Types[edit]. Ribonucleases[edit]. The trans-form (two separate strands) of the 17E DNAzyme. Most ribonuclease DNAzymes have a ... Methods[edit]. Main article: Systematic evolution of ligands by exponential enrichment. in vitro selection[edit]. Because there ... Applications[edit]. Although RNA enzymes were discovered before DNA enzymes, the latter have some distinct advantages. DNA is ...
RNA Oncoviruses[edit]. Brief history[edit]. In the 1960s, the replication process of RNA virus was believed to be similar to ... RNA viruses[edit]. Not all oncoviruses are DNA viruses. Some RNA viruses have also been associated such as the hepatitis C ... Single-stranded RNA replication involves RNA-dependent RNA synthesis which meant that virus-coding enzymes would make partial ... Classification[edit]. DNA viruses[edit]. *Human papilloma virus (HPV), a DNA virus, causes transformation in cells through ...
RNA is multifunctional[edit]. RNA is multifunctional, its primary function is to encode proteins, according to the instructions ... See also[edit]. *List of biophysically important macromolecular crystal structures. References[edit]. *^ a b c d e Stryer L, ... DNA, RNA, and proteins all consist of a repeating structure of related building blocks (nucleotides in the case of DNA and RNA ... The single-stranded nature of RNA, together with tendency for rapid breakdown and a lack of repair systems means that RNA is ...
1993). "On the evolution of RNA editing". Trends in Genetics. 9 (8): 265-268. doi:10.1016/0168-9525(93)90011-6.. ... RNA editing may have arisen in Trypanosoma brucei.[21][24][23][25][26] ... References[edit]. *^ Werner, Andreas; Piatek, Monica J.; Mattick, John S. (April 2015). "Transpositional shuffling and quality ... Types of trends in complexity[edit]. Passive versus active trends in complexity. Organisms at the beginning are red. Numbers ...
Jin Y, Zhang W, Li Q (June 2009). "Origins and evolution of ADAR‐mediated RNA editing". IUBMB Life. 61 (6): 572-578. doi: ... TEs also serve to generate repeating sequences that can form dsRNA to act as a substrate for the action of ADAR in RNA editing ... Class I TEs are copied in two stages: first, they are transcribed from DNA to RNA, and the RNA produced is then reverse ... References[edit]. *^ Bourque G, Burns KH, Gehring M, Gorbunova V, Seluanov A, Hammell M, et al. (November 2018). "Ten things ...
... a high-affinity kainate receptor with novel potential RNA editing sites". Recept. Channels. 2 (4): 315-26. PMID 7719709.. ... References[edit]. *^ a b c GRCh38: Ensembl release 89: ENSG00000163873 - Ensembl, May 2017 ... Further reading[edit]. *. Nutt SL, Hoo KH, Rampersad V, et al. (1995). "Molecular characterization of the human EAA5 (GluR7) ... External links[edit]. *GRIK3 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH) ...
The pre-mRNA of the ARL6IP4 gene product is subject to RNA Editing. A to I RNA editing is catalyzed by a family of adenosine ... "Screening of human SNP database identifies recoding sites of A-to-I RNA editing". RNA. 14 (10): 2074-85. doi:10.1261/rna.816908 ... The region that base pairs with the editing region is known as an Editing Complementary Sequence (ECS). Editing occurs at a K/R ... editing is unusual as the RNA fold back structure is made up off exonic sequence only. Editing at this site results in a codon ...
RNA virus recombinationEdit. Numerous RNA viruses are capable of genetic recombination when at least two viral genomes are ... Mechanism of RNA recombination in carmo- and tombusviruses: evidence for template switching by the RNA-dependent RNA polymerase ... When replicating its (+)ssRNA genome, the poliovirus RNA-dependent RNA polymerase (RdRp) is able to carry out recombination. ... ReferencesEdit. *^ a b Rieger R. Michaelis A., Green M. M. (1976). Glossary of genetics and cytogenetics: Classical and ...
tRNA biogenesisEdit. In eukaryotic cells, tRNAs are transcribed by RNA polymerase III as pre-tRNAs in the nucleus.[50] RNA ... A transfer RNA (abbreviated tRNA and formerly referred to as sRNA, for soluble RNA[1]) is an adaptor molecule composed of RNA, ... doi:10.4161/rna.27177. PMC 3917982 . PMID 24351723.. *^ a b Shigematsu Megumi; et al. (2014). "Transfer RNA as a source of ... doi:10.1261/rna.5142404. PMC 1370521 . PMID 14681588.. *^ a b Agirrezabala X, Frank J; Frank (2009). "Elongation in translation ...
DNA and RNA synthesisEdit. ATP is one of four "monomers" required in the synthesis of RNA. The process is promoted by RNA ... Production from AMP and ADPEdit. Production, aerobic conditionsEdit. With a typical intracellular concentration of 1-10 mM, ATP ... Other biochemical functionsEdit. Intracellular signalingEdit. ATP is involved signal transduction by serving as substrate for ... ReferencesEdit. *^ Knowles, J. R. (1980). "Enzyme-catalyzed phosphoryl transfer reactions". Annu. Rev. Biochem. 49: 877-919. ...
transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding. • RNA ... References[edit]. *^ a b c GRCh38: Ensembl release 89: ENSG00000175879 - Ensembl, May 2017 ... negative regulation of transcription from RNA polymerase II promoter. • positive regulation of transcription from RNA ... RNA polymerase II regulatory region sequence-specific DNA binding. • DNA binding. • sequence-specific DNA binding. • ...
Finding the virus, viral RNA, or antibodies in blood[1]. Differential diagnosis. Malaria, cholera, typhoid fever, meningitis, ... This page was last edited on 19 October 2020, at 17:42 (UTC). ... detecting the viral RNA by polymerase chain reaction (PCR)[6][ ... Ebolaviruses contain single-stranded, non-infectious RNA genomes.[46] Ebolavirus genomes contain seven genes including 3'-UTR- ... The specific diagnosis of EVD is confirmed by isolating the virus, detecting its RNA or proteins, or detecting antibodies ...
References[edit]. *^ a b c GRCh38: Ensembl release 89: ENSG00000109158 - Ensembl, May 2017 ... External links[edit]. *GABRA4+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH) ... This page was last edited on 22 August 2019, at 00:56 (UTC). ... RNA expression pattern. More reference expression data. Gene ...
RNA editing in plastidsEdit. RNA editing is the insertion, deletion, and substitution of nucleotides in a mRNA transcript prior ... DNA replicationEdit. Leading model of cpDNA replicationEdit. Chloroplast DNA replication via multiple D loop mechanisms. ... Protein synthesisEdit. See also: Transcription and translation. Protein synthesis within chloroplasts relies on an RNA ... Takenaka M, Zehrmann A, Verbitskiy D, Härtel B, Brennicke A (2013). "RNA editing in plants and its evolution". Annual Review of ...
References[edit]. Footnotes[edit]. *^ Andrew does not usually use a surname but when one is needed, it is Mountbatten-Windsor.[ ... In late 1983, Prince Andrew transferred to RNAS Portland, was trained to fly the Lynx helicopter, and was promoted to the rank ... Personal life[edit]. Relationship with Koo Stark[edit]. Prince Andrew met Koo Stark in February 1981, and they were close for ... Military service[edit]. Royal Navy[edit]. The Royal Household announced in November 1978 that Prince Andrew would join the ...
On 18 May 2012 it flew the Olympic flame from Athens International Airport to RNAS Culdrose while carrying various dignitaries ... This page was last edited on 19 June 2021, at 07:37 (UTC). ...
RNA polymerase II core promoter sequence-specific DNA binding. • RNA polymerase II transcription factor activity, sequence- ... ReferencesEdit. *^ a b c GRCh38: Ensembl release 89: ENSG00000125618 - Ensembl, May 2017 ... transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding. • RNA polymerase ... FunctionEdit. This gene is a member of the paired box (PAX) family of transcription factors. Members of this gene family ...
References[edit]. *^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad "Lassa fever". WHO. March 2016. Archived ... and bi-segmented RNA. This virus has a both a large and a small genome section, with four lineages identified to date: Josiah ( ... Virology[edit]. Lassa virus is a member of the Arenavirida family of viruses.[7] Specifically it is an old world arenavirus, ... Research[edit]. The Lassa virus is one of several viruses identified by WHO as a likely cause of a future epidemic. They ...
LigandsEdit. AgonistsEdit. *Endogenous progestogens (e.g., progesterone). *Synthetic progestogens (e.g., norethisterone, ... RNA polymerase II transcription factor activity, sequence-specific DNA binding. • transcriptional activator activity, RNA ... ReferencesEdit. *^ a b c GRCh38: Ensembl release 89: ENSG00000082175 - Ensembl, May 2017 ... AntagonistsEdit. *Antiprogestogens (e.g., mifepristone, aglepristone, onapristone, lonaprisan, lilopristone, toripristone)[20] ...
ReferencesEdit. *^ a b c d Oldstone, Michael (2009). Viruses, Plagues, and History: Past, Present and Future. Oxford University ... "An RNA Pseudoknot Is Required for Production of Yellow Fever Virus Subgenomic RNA by the Host Nuclease XRN1". Journal of ... AsiaEdit. The main vector (A. aegypti) also occurs in tropical and subtropical regions of Asia, the Pacific, and Australia, but ... PathogenesisEdit. After transmission from a mosquito, the viruses replicate in the lymph nodes and infect dendritic cells in ...
See also[edit]. *Endospore staining. References[edit]. *^ Murray, Patrick R.; Ellen Jo Baron (2003). Manual of Clinical ... and the sigma factor subunits of RNA polymerase. ... External links[edit]. Wikimedia Commons has media related to ... Biotechnology[edit]. Bacillus subtilis spores are useful for the expression of recombinant proteins and in particular for the ... Structure[edit]. Variations in endospore morphology: (1, 4) central endospore; (2, 3, 5) terminal endospore; (6) lateral ...
Clinical significance[edit]. Beta-amyloid production[edit]. Transgenic mice that over-expressed mutant presenilin-1 show an ... negative regulation of transcription from RNA polymerase II promoter. • proteolysis. • regulation of synaptic plasticity. • ... References[edit]. *^ a b c GRCh38: Ensembl release 89: ENSG00000080815 - Ensembl, May 2017 ... Cancer[edit]. In addition to its role in Alzheimer's disease, presenilin-1 also found to be important in cancer. A study of ...
Notes and references[edit]. *^ a b c d "Types of Inhibition". NIH Center for Translational Therapeutics. Archived from the ... so it cannot synthesize DNA and RNA.[3] Thus, the cancer cells are unable to grow and divide. Another example involves ... Equation[edit]. The Michaelis-Menten Model can be an invaluable tool to understanding enzyme kinetics. According to this model ... Biological Examples[edit]. After an accidental ingestion of a contaminated opioid drug desmethylprodine, the neurotoxic effect ...
References[edit]. *^ a b c GRCh38: Ensembl release 89: ENSG00000051180 - Ensembl, May 2017 ... messenger RNA. [13]. Breast cancer (progesteron receptor negative). Over-expression. -. messenger RNA. [16]. ... Family[edit]. In mammals, seven recA-like genes have been identified: Rad51, Rad51L1/B, Rad51L2/C, Rad51L3/D, XRCC2, XRCC3, and ... Pathology[edit]. This protein is also found to interact with PALB2[10] and BRCA2, which may be important for the cellular ...
SportEdit. FootballEdit. During the 2016-17 season, the region had one Premier League team (A.F.C. Bournemouth), and seven ... Fourth Element (wet suits) are on the A3083 at Cury, south of RNAS Culdrose and Helston. A.P. Valves make diving equipment in ... EducationEdit. SchoolsEdit. See also: List of schools in England § South West of England ... ReferencesEdit. *^ "South West had the oldest population in the UK in 2012". Office for National Statistics. 17 October 2013. ...
Amino acids[edit]. BMAA[edit]. The non-proteinogenic amino acid beta-Methylamino-L-alanine (BMAA) is ubiquitously produced by ... is toxic to liver and kidney tissue and is thought to inhibit protein synthesis and to covalently modify DNA and/or RNA. There ... References[edit]. *^ a b Stewart I, Seawright AA, Shaw GR (2008). Cyanobacterial poisoning in livestock, wild mammals and birds ... Cyclic peptides[edit]. A peptide is a short polymer of amino acids linked by peptide bonds. They have the same chemical ...
EcologyEdit. HabitatsEdit. Archaea that grow in the hot water of the Morning Glory Hot Spring in Yellowstone National Park ... Archaea were split off as a third domain because of the large differences in their ribosomal RNA structure. The particular RNA ... ReferencesEdit. *^ a b c Woese, C.R.; Kandler, O.; Wheelis, M.L. (1990). "Towards a natural system of organisms: proposal for ... MembranesEdit. Membrane structures. Top, an archaeal phospholipid: 1, isoprene chains; 2, ether linkages; 3, L-glycerol moiety ...
Genes[edit]. Number of genes[edit]. The following are some of the gene count estimates of human chromosome 16. Because ... SNORD71: encoding protein Small nucleolar RNA, C/D box 71. *SPSB3: encoding protein SplA/ryanodine receptor domain and SOCS box ... Associated traits[edit]. *Red hair. Cytogenetic band[edit]. @media all and (max-width:720px){.mw-parser-output .tmulti>. ... References[edit]. *^ "Human Genome Assembly GRCh38 - Genome Reference Consortium". National Center for Biotechnology ...
Structure[edit]. Sequence and prevalence[edit]. Figure 2. Mechanism for transcription initiation at the TATA box. Transcription ... the TATA box is found at RNA polymerase II promoter regions, although some in vitro studies have demonstrated that RNA ... History[edit]. Discovery[edit]. The TATA box was the first eukaryotic core promoter motif to be identified in 1978 by American ... Function[edit]. Role in transcription initiation[edit]. The TATA-box is the site of preinitiation complex formation, which is ...
Chemistry of histone modifications[edit]. Lysine methylation[edit]. The addition of one, two, or many methyl groups to lysine ... where it is initiated by recruitment of the RNA-induced transcriptional silencing (RITS) complex to double stranded RNAs ... Function [edit]. Compacting DNA strands[edit]. Histones act as spools around which DNA winds. This enables the compaction ... Other functions[edit]. DNA damage[edit]. Marking sites of DNA damage is an important function for histone modifications. It ...
ReferencesEdit. *^ a b c d e Fürtig, Boris; Richter, Christian; Wöhnert, Jens; Schwalbe, Harald (2003). "NMR Spectroscopy of ... such as DNA or RNA. It is useful for molecules of up to 100 nucleotides, and as of 2003, nearly half of all known RNA ... HistoryEdit. Nucleic acid NMR studies were performed as early as 1971,[8] and focused on using the low-field imino proton ... Experimental methodsEdit. Two-dimensional NMR methods are almost always used with nucleic acids. These include correlation ...
RNA interference (RNAi) and small-RNA biology; DNA replication; RNA splicing; signal transduction; genome structure; non-coding ... Contemporary research[edit]. This section relies too much on references to primary sources. Please improve this section by ... Notes and references[edit]. *^ National Park Service (2009-03-13). "National Register Information System". National Register of ... Funding[edit]. In 2015, CSHL had an operating budget of $150 million, over $100 million of which was spent on research.[17] ...
原生質絲可以讓蛋白質(包括轉錄因子)、小干擾RNA、mRNA和病毒的基因組在細胞內流通。其中一個病毒的運動蛋白例子是MP-30。MP-30可結合病毒的基因組,並且將病毒的
ReferencesEdit. *^ a b "International Stratigraphic Chart". International Commission on Stratigraphy. Archived from the ... The first life forms and self-replicating RNA molecules evolve around 4,000 Ma, after the Late Heavy Bombardment ends on Earth ... RationaleEdit. Evidence from radiometric dating indicates that Earth is about 4.54 billion years old.[3][4] The geology or deep ... TerminologyEdit. The primary defined divisions of time are eons, in sequence the Hadean, the Archean, the Proterozoic and the ...
Early life and education[edit]. Hall was born in Barnsley. He earned his BA in chemistry from Oxford University. He began his ... evidence of the importance of Ral was provided when cortical neurons were depleted of endogenous RalA and RalB isoforms by RNA ... Career and research[edit]. Hall's PhD was on the enzymology of B-lactamase, which led to his first paper being published in ... Honours and awards[edit]. In 1993, Alan Hall was awarded the Feldberg Foundation Prize for his work on the role GTP-binding ...
In eukaryotesEdit. Structure of eukaryotic RNA polymerase II (light blue) in complex with α-amanitin (red), a strong poison ... Non-coding RNA or "RNA genes". These are a broad class of genes that encode RNA which is not translated into protein. The most ... RNA polymerase IV synthesizes siRNA in plants.[5]. *RNA polymerase V synthesizes RNAs involved in siRNA-directed ... RNA polymerase III synthesizes tRNAs, rRNA 5S and other small RNAs found in the nucleus and cytosol.[4] ...
See also[edit]. *Neutral theory of molecular evolution. References[edit]. *^ a b c d e f g Watson JD, Baker TA, Bell SP, Gann A ... A fundamental building block of RNA structure crucial to RNA function in diverse biological systems". EMBO Rep. 1 (1): 18-23. ... Terminology[edit]. A position of a codon is said to be a n-fold degenerate site if only n of four possible nucleotides (A, C, G ... Background[edit]. Degeneracy of the genetic code was identified by Lagerkvist.[2] For instance, codons GAA and GAG both specify ...
Complex management: RNA editing in trypanosomes.. Stuart KD1, Schnaufer A, Ernst NL, Panigrahi AK. ... Most mitochondrial mRNAs in kinetoplastids require editing, that is, the posttranscriptional insertion and deletion of uridine ... shows that the complex that catalyzes the central steps of editing is partitioned into distinct insertion and deletion editing ... nucleotides that are specified by guide RNAs and catalyzed by multiprotein complexes. Recent studies have identified many of ...
... strategy can be used to precisely mimic human pathologies by efficiently inducing nonsense or missense mutations as well as RNA ... Highly efficient RNA-guided base editing in rabbit. *Zhiquan Liu1. na1, ... 1a). Base editing was conducted in rabbit zygotes by microinjection of BE3-encoding mRNA and single guide RNAs (sgRNAs). Sanger ... Highly efficient RNA-guided base editing in mouse embryos. Nat. Biotechnol. 35, 435-437 (2017). ...
RNA editing has been reported in viruses and diverse eukaryotes. In flowering plants, RNA editing converts cytidines to ... They report that in norflurazon-treated seedlings, RNA editing is altered at 21 sites and that GUN1 affects RNA editing at 11 ... In these cells, GUN1 accumulates and regulates RNA editing by interacting with MORF2 (red arrow). Abnormal RNA editing ... an essential chloroplast protein and a core component of the RNA editosome that edits many of the RNAs that are edited in ...
A powerful scientific tool for editing the DNA instructions in a genome can now also be applied to RNA as Berkeley Lab ... researchers have demonstrated a means by which the CRISPR/Cas9 protein complex can be programmed to recognize and cleave RNA at ... RCas9: A programmable RNA editing tool. DOE/Lawrence Berkeley National Laboratory. Journal. Nature. Funder. National Institutes ... A powerful scientific tool for editing the DNA instructions in a genome can now also be applied to RNA, the molecule that ...
RNA Editing for Specific C to U Exchange), that expands CRISPRs RNA editing capabilities. ... New CRISPR platform expands RNA editing capabilities The new system, dubbed RESCUE, allows RNA edits to be made that were not ... Expanding the reach of RNA editing to new targets. The previously developed REPAIR platform used the RNA-targeting CRISPR/Cas13 ... RESCUE can be guided to any RNA of choice, then perform a C-to-U edit through the evolved ADAR2 component of the platform. The ...
The mutation that causes Rett Syndrome can be corrected in the brains of mice using an RNA editing technique that repairs the ... As the RNA editing approach progresses through experimental steps, additional questions will need to be answered. "We need to ... They asked three questions: Is it possible to edit MeCP2 RNA in several different types of neurons in adult mice in vivo? If so ... As a strategy to restore the normal function of MECP2, the single-base RNA editing approach of swapping out A and G could ...
By comparing DNA and RNA sequences from the squid brain, the team found that 60 percent of the RNA transcripts had been edited ... RNA editing was thought to be sparingly used, based on a limited number of studies in mammals and flies. But recently, MBL ... "In squid, RNA editing is so pervasive that the central dogma should be modified to include this process," Rosenthal says. " ... Alon S et al (2015) The majority of transcripts in the squid nervous system are extensively recoded by A-to-I RNA editing. ...
The most common type of RNA editing is A-to-I editing by double-stranded RNA-specific adenosine deaminase (ADAR) enzymes. ... RNA editing is unique among these modifications because it not only alters the cellular fate of RNA molecules but also alters ... Editing of these non-coding sites is thought to have a critical role in protecting against activation of innate immunity by ... The results have changed our understanding of the extent and distribution of A-to-I editing and its role in evolution and ...
RNA editing in the 3-untranslated region has been shown to be the alteration that most frequently leads to changes in RNA ... RNA and protein levels in cancer tissues to substantiate further the diagnostic potential of RNA editing. ... deepens our understanding of tissue-specific regulation of programmed alteration of RNA, known as RNA editing, in the intestine ... Deletion of the RNA-editing enzyme Apobec-1 in this model drastically reduces the number of polyps in the intestine. The ...
Because A-to-I editing may affect ba ... Control of ADAR1 Editing of Hepatitis Delta Virus RNAs John L. ... Because A-to-I editing may affect base-pairing and RNA structure, processes including translation, splicing, RNA replication, ... Editing of Neurotransmitter Receptor and Ion Channel RNAs in the Nervous System ... increasingly apparent that ADARs may possess roles not only as enzymes that deaminate adenosine to produce inosine in RNA ...
RNA Editors, Cofactors, and mRNA Targets: An Overview of the C-to-U RNA Editing Machinery and Its Implication in Human Disease ... Loss of APOBEC1 RNA-editing function in microglia exacerbates age-related CNS pathophysiology. Author(s): Daniel C. Cole, ... A New Chapter in Genetic Medicine: RNA Editing and its Role in Disease Pathogenesis. Author(s): Khatuna Gagnidze, Violeta Rayon ... MultiEditR: An easy validation method for detecting and quantifying RNA editing from Sanger sequencing. Author(s): Mitchell ...
Orthogonal Cas9 proteins for RNA-guided gene regulation and editing.. Esvelt KM1, Mali P, Braff JL, Moosburner M, Yaung SJ, ... Cas9-mediated gene editing in human cells. (a) A homologous recombination assay was used to quantify gene editing efficiency. ... protein from the Streptococcus pyogenes CRISPR-Cas acquired immune system has been adapted for both RNA-guided genome editing ... We provide a basal set of orthogonal RNA-guided proteins for controlling biological systems and establish a general methodology ...
Date: 2019-09-26, Time: 15:00:00, Speaker: Heather Hundley, Location: IMP Lecture Hall, Type: DK RNA Biology Seminar, Institute ...
NF treatment also affected RNA editing in plastids (16, 17). RNA editing is a posttranscriptional modification of RNA that ... In this study, we have discovered an unexpected role for GUN1 in plastid RNA editing, as gun1 mutations affect RNA-editing ... GUN1 plays a direct role in RNA editing by physically interacting with MULTIPLE ORGANELLAR RNA EDITING FACTOR 2 (MORF2). MORF2 ... How might a change in RNA editing trigger a retrograde signaling pathway? Among the editing sites that exhibit similar editing- ...
In fact, they found over 500,000 sites in coral genes where the sequence had been altered with RNA editing. The RNA editing ... A common type of RNA editing in animal cells involves the alteration of an adenosine base to an inosine base (A-to-I editing). ... it turns out that the bases in the RNA can be changed dynamically on the fly in a fine-tuning process called RNA editing. ... A-to-I RNA Editing in the Earliest-Diverging Eumetazoan Phyla. Molecular Biology and Evolution. 34 (8): 1890-1901. ...
... 17.11.2015. CRISPR/Cas9 gene editing technique can be transiently ... An initial, specially modified RNA is used to replace the usual guide RNA. This RNA directs Cas9s DNA-cutting activity to a ... Activity is transient, however, as the editing stops when the guiding RNA drug is cleared. An extension of the approach can ... The new approach introduces chemically modified, RNA-based drugs to transiently activate the CRISPR/Cas9 gene editing system. ...
CRISPR is a new affordable genome editing tool enabling access to genome editing for all. ... Purified RNA-only guide RNA. *Ready-to-use gRNAs in a purified RNA format suitable for microinjection or cell culture. ... All-in-one, ready-to-use Cas9 and guide RNA (gRNA) expression plasmids. CRISPR paired nickases. Purified RNA-only guide RNA. ... has allowed for the development for an RNA-guided genome editing tool that is simple, easy and quick to implement. The CRISPR ...
... Posted: Jun 6 2016, 7:59am CDT , by Sumayah Aamir, Updated: Jun 6 2016, 8 ... This RNA part of CRISPR technology was pioneered at MIT. It has its basis firmly embedded in C2c2 which is a special enzyme, ... RNA, as everyone knows, helps change genes into proteins that can be utilized. Were this methodology to become the norm, cancer ... It is being said that CRISPR gene-editing technology may spell the end of many ailments such as Huntingtons Disease. The ...
Broad Institute scientists have created a CRISPR-based method that targets RNA in a way that makes reversible changes to DNA ... CRISPR-Cas9 gene editing has been useful for blocking specific genes to correct mutations, but it makes permanent changes to ... RNA Editing for Programmable A to I Replacement) can edit single nucleosides, or the "letters" that make up the RNA helix. ... causing the RNA to clump together in cells. The RNA-targeted CRISPR managed to clear the majority of clumps and errant RNA ...
RNA editing targets single bases. One of the most common types of RNA editing in animals involves the changing of an adenosine ... RNA Biol. 7 (2): 205-212.. * Nishikura, K. 2010. Functions and regulation of RNA editing by ADAR deaminases. Annu Rev Biochem. ... it has also been discovered that another form of dynamic RNA alteration exists called RNA editing. Unlike alternative splicing ... This type of editing in both coding and non-coding RNAs has been found to have profound effects on gene expression.3 In ...
A-to-I RNA editing) is an important mechanism that increases transciptome diversity. It occurs when a genomically encoded ... Adenosine-to-inosine modification of RNA molecules (A-to-I RNA editing) is an important mechanism that increases transciptome ... However, such methods perform poorly on RNAs that underwent extensive editing ("ultra"-editing), as the large number of ... Identification of widespread ultra-edited human RNAs PLoS Genet. 2011 Oct;7(10):e1002317. doi: 10.1371/journal.pgen.1002317. ...
... - PubMed - NCBI. Abstract. CRISPR-Cas base ... CBE-induced RNA edits occur in both protein-coding and non-protein-coding sequences and generate missense, nonsense, splice ... These variants also showed more precise on-target DNA editing than the wild-type CBE and, for most guide RNAs tested, no ... Finally, we show that an adenine base editor7 can also induce transcriptome-wide RNA edits. These results have implications for ...
In addition to RNA editing, additional functions have been proposed for ADAR1. To determine the specific role of RNA editing by ... RNA editing helps identify cellular RNAs. Adenosine bases in messenger RNA (mRNAs) can be enzymatically modified and changed ... The principal RNA-editing enzyme modifies cellular RNAs to prevent their erroneous identification as foreign RNA. ... The principal RNA-editing enzyme modifies cellular RNAs to prevent their erroneous identification as foreign RNA. ...
The Liu lab found a way to make edits without causing double-strand DNA breaks while the Zhang lab created an RNA editor that ... While DNA editing holds promise for treating genetic disease, temporary editing of RNA has potential for treating diseases ... called RNA Editing for Programmable A to I Replacement (REPAIR), which allows for the temporary repair of single RNA ... one for editing point mutations in the genome and the other for editing RNA, they revealed today in separate studies. ...
Expanding the reach of RNA editing to new targets. The previously developed REPAIR platform used the RNA-targeting CRISPR/Cas13 ... RESCUE can be guided to any RNA of choice, then perform a C-to-U edit through the evolved ADAR2 component of the platform. The ... A major advantage of RNA editing is its reversibility, in contrast to changes made at the DNA level, which are permanent. Thus ... In addition, some cell types, such as neurons, are difficult to edit using CRISPR/Cas9-mediated editing, and new strategies are ...
Researchers found that both CBEs and ABEs can cause transcriptome-wide RNA edits, which has implications for the research and ... CRISPR-Cas Base Editing Technology Can Cause Transcriptome-Wide RNA Off-Target Edits. Apr 17, 2019 ... Home » CRISPR-Cas Base Editing Technology Can Cause Transcriptome-Wide RNA Off-Target Edits ... Joung has reported in a new study that CRISPR-Cas base editing technology can induce transcriptome-wide off-target RNA editing ...
Broad Institute researchers have developed a new strategy for editing RNA they believe could someday be used to treat brain ... Another advantage of RNA editing is that it can be reversed. The MIT researchers showed in their study that they could use ... CRISPR editing of DNA uses the enzyme Cas9 to snip DNA at specific locations. Targeting RNA instead can offer some advantages, ... Now, Zhang is rolling out his latest invention-a new strategy for editing RNA that his team says could someday be used to treat ...
RNA editing may include the insertion, deletion, and base substitution of nucleotides within the RNA molecule. RNA editing is ... the effects of RNA editing − including potential off-target mutations in RNA − are transient and are not inherited. RNA editing ... RNA editing is used for stability and generation of protein variants. Viral RNAs are transcribed by a virus-encoded RNA- ... Therefore, a RNA transcript requiring extensive editing will need more than one guide RNA and editosome complex. The editing ...
... system promise an improved approach to genome editing. However, the applicability and efficiency of this system in model ... Genome editing with RNA-guided Cas9 nuclease in zebrafish embryos Cell Res. 2013 Apr;23(4):465-72. doi: 10.1038/cr.2013.45. ... Here, we report that RNA-guided Cas9 nuclease efficiently facilitates genome editing in both mammalian cells and zebrafish ... system promise an improved approach to genome editing. However, the applicability and efficiency of this system in model ...
Loss of Fmrp resulted in a mild increase in RNA editing in the coding sequences of conserved synaptic genes. These findings ... Thus, we characterized global RNA editing in the zebrafish transcriptome and used a microfluidic-based high-throughput ... The genetic cause of this disorder is the silencing of the fmr1 gene, which encodes the RNA-binding protein Fmrp. This protein ... propose that altered RNA editing levels may affect neuronal and behavioral deficiencies in FXS. ...
  • RESCUE builds on REPAIR, a technology developed by Zhang's team that changes adenine bases into inosine in RNA. (eurekalert.org)
  • The previously developed REPAIR platform used the RNA-targeting CRISPR/Cas13 to direct the active domain of an RNA editor, ADAR2, to specific RNA transcripts where it could convert the nucleotide base adenine to inosine, or letters A to I. Zhang and colleagues took the REPAIR fusion, and evolved it in the lab until it could change cytosine to uridine, or C to U. (eurekalert.org)
  • When an adenosine in NEIL1 messenger RNA gets deaminated to form inosine, the mRNA is subsequently translated to place an arginine instead of a lysine in the portion of NEIL1 that recognizes oxidized DNA bases. (acs.org)
  • It also is becoming increasingly apparent that ADARs may possess roles not only as enzymes that deaminate adenosine to produce inosine in RNA substrates with double-stranded character, but also as proteins independent of their catalytic property. (springer.com)
  • A common type of RNA editing in animal cells involves the alteration of an adenosine base to an inosine base (A-to-I editing). (icr.org)
  • The RNA-targeting, CRISPR-based tool, REPAIR currently swaps out the RNA base adenosine for inosine. (fiercebiotech.com)
  • One of the most common types of RNA editing in animals involves the changing of an adenosine base to an inosine base (A-to-I editing). (icr.org)
  • 2010. Proteome diversification by adenosine to inosine RNA editing. (icr.org)
  • 2013. Adenosine-to-inosine RNA editing and human disease. (icr.org)
  • Adenosine-to-inosine modification of RNA molecules (A-to-I RNA editing) is an important mechanism that increases transciptome diversity. (nih.gov)
  • Adenosine bases in messenger RNA (mRNAs) can be enzymatically modified and changed into inosine bases. (sciencemag.org)
  • Adenosine-to-inosine (A-to-I) editing is a highly prevalent posttranscriptional modification of RNA, mediated by ADAR (adenosine deaminase acting on RNA) enzymes. (sciencemag.org)
  • The deamination of adenine results in inosine, which is treated as guanine by DNA and RNA polymerases. (genomeweb.com)
  • It transforms A to inosine, which is read as G. Similar to the BE3 base editor, the ABE also contains a nickase which causes the non-edited DNA strand to replace the T with a C. The CRISPR-Cas9 contained in the system binds to the guide RNA, and guides the ABE to the editing site - however, it has been impaired so that it can no longer induce DSBs. (genomeweb.com)
  • The diversity of RNA editing phenomena includes nucleobase modifications such as cytidine (C) to uridine (U) and adenosine (A) to inosine (I) deaminations, as well as non-template nucleotide additions and insertions. (wikipedia.org)
  • Adenosine-to-inosine (A-to-I) RNA editing leads to transcriptome diversity and is important for normal brain function. (sciencemag.org)
  • Adenosine-to-inosine (A-to-I) RNA editing converts a genomically encoded adenosine (A) into inosine (I), which in turn is read as guanosine (G), and increases transcriptomic diversity ( 1 , 2 ). (sciencemag.org)
  • ADAR is the enzyme responsible for adenosine-to-inosine (A-to-I) RNA editing. (scienceboard.net)
  • In human, the most common RNA editing event involves the deamination of adenosine (A) into inosine (I) through the adenosine deaminase acting on RNA proteins. (frontiersin.org)
  • 5] Gria2 pre-mRNA undergoes a type of editing called adenosine-to-inosine (A-to-I) editing. (wikipedia.org)
  • ADARs deaminate adenosine bases to inosine bases in a site-specific manner in double-stranded RNA substrates (dsRNA). (wikipedia.org)
  • Catalytic deamination of adenosine (A) to inosine (I) on RNA molecules is a fundamental cellular mechanism that directly impacts expression and function of a large set of proteins. (springer.com)
  • Adenosine deaminases acting on RNA (ADARs) convert adenosine to inosine in double-stranded RNA (dsRNA). (mdpi.com)
  • Epitranscriptomic events such as adenosine-to-inosine (A-to-I) RNA editing by ADAR can recode mRNAs to translate novel proteins. (medworm.com)
  • Bar-Eli identified adenosine-to-inosine RNA editing in three miRNAs. (healthcanal.com)
  • One type involves the deamination of cytidine (C) to create uridine (U), and the other, deamination of adenosine (A) to create inosine (I). This review focuses on the type of editing that occurs by adenosine deamination to change A to I in the nuclear-encoded RNAs of metazoa. (pubmedcentralcanada.ca)
  • ADARs act on RNA that is completely, or largely, double-stranded and catalyze the deamination of adenosine to produce inosine ( Figure 1 ). (pubmedcentralcanada.ca)
  • In addition, because inosine base-pairs with cytidine, ADARs can change the structure of an RNA by changing an AU base-pair to an IU mismatch. (pubmedcentralcanada.ca)
  • Recently, adenosine (A)-to-inosine (I) RNA editing has been shown to be a potential epigenetic event in human cancers. (aacrjournals.org)
  • Deamination type editing, on the other hand, changes the identity of a base by deaminating cytidine to uracil or adenosine to inosine, respectively ( Carter, 1995 ). (frontiersin.org)
  • ADAR (adenosine deaminase acting on RNA) is an RNA editing enzyme that targets both coding and noncoding dsRNAs (double stranded RNAs) and converts adenosine to inosine, which is read by translation machinery and by polymerases during RNA-dependent RNA replication as if it is guanosine. (paper.edu.cn)
  • The Axiomer® "Editing Oligo Nucleotides", or EONs, recruit an endogenously expressed RNA editing system called ADAR, which it can direct to change an Adenosine (A) to an Inosine (I) in the RNA - an Inosine is translated as a Guanosine (G). (pharmiweb.com)
  • Adenosine deaminase acting on RNA-2 (ADAR2) enzyme catalyzes adenosine-to-inosine (A-to-I) RNA editing of mRNAs and microRNAs and controls brain development. (ahajournals.org)
  • RNA editing is a regulatory mechanism in which nucleotides are altered posttranscriptionally and most frequently involves conversion of adenosine to inosine, which is recognized as a guanosine during translation. (aacrjournals.org)
  • Chen and colleagues performed RNA sequencing analysis to identify molecular changes in hepatocellular carcinoma (HCC) samples that might contribute to disease progression, and they detected elevated adenosine-to-inosine RNA editing of antizyme inhibitor 1 ( AZIN1 ) in HCC samples compared with adjacent normal tissues. (aacrjournals.org)
  • The most common modification is the editing of an adenosine to inosine (A-to-I) thus fooling the ribosome to think it is translating a guanine. (arvojournals.org)
  • Among the various types of RNA editing, adenosine-to-inosine (A-to-I) RNA editing is the most frequent type of RNA editing in mammals. (ovid.com)
  • Design By utilising large scale transcriptome sequencing of three paired HCC clinical specimens and their adjacent non-tumour (NT) tissue counterparts at depth, we discovered an average of 20 007 inferred A to I (adenosine to inosine) RNA editing events in transcripts. (bmj.com)
  • The presence of these long intramolecular dsRNA structures within 3′-UTRs decreases translational efficiency, and although the structures undergo extensive editing in vivo, the effects on translation are independent of the presence of inosine. (iu.edu)
  • The primary transcripts of miRNAs contain double-stranded RNA and are therefore potential substrates for adenosine to inosine (A-to-I) RNA editing. (biomedcentral.com)
  • Most RNA editing in human cells is adenosine to inosine (A-to-I) RNA editing which involves the conversion of A-to-I in dsRNA [ 25 , 26 ]. (biomedcentral.com)
  • Adenosine deaminase acting on dsRNA (ADAR1) isoforms neutralize the immunostimulatory activity of double-stranded RNA (dsRNA) by converting adenosine to inosine (i.e. (elifesciences.org)
  • High throughput (HTP) sequencing analysis have revealed that adenosine to inosine RNA editing is a more common event in the human transcriptome than previously anticipated. (neurodegenerationresearch.eu)
  • Adenosine to inosine (A-to-I) RNA editing is a post-transcriptional modification catalyzed by the ADAR (adenosine deaminase that acts on RNA) enzymes, which are ubiquitously expressed among metazoans. (biomedcentral.com)
  • Adenosine-to-inosine (A-to-I) RNA editing is a fundamental post-transcriptional gene regulatory mechanism, diversifying the transcriptome of Metazoa [ 1 , 2 ]. (biomedcentral.com)
  • Editing of messenger RNA precursors and of tRNAs by adenosine to inosine conversion. (surrey.ac.uk)
  • The double-stranded RNA-specific adenosine deaminases ADAR1 and ADAR2 convert adenosine (A) residues to inosine (I) in messenger RNA precursors (pre-mRNA). (surrey.ac.uk)
  • Adenosine-to-inosine (A-to-I) RNA editing is a process that contributes to the diversification of proteins that has been shown to be essential for neurotransmission and other neuronal functions. (biomedcentral.com)
  • Adenosine-to-inosine (A-to-I) RNA editing of double-stranded RNA (dsRNA), catalyzed by adenosine deaminase acting on RNA (ADAR) protein family, is an essential event for the proper functioning of the mammalian brain [ 1 ]. (biomedcentral.com)
  • Thus adenosine-to-inosine RNA editing can respond to the physical environment. (mysciencework.com)
  • Until now, it was thought that Cas9 could not be used on the RNA molecules that transcribe those DNA instructions into the desired proteins. (eurekalert.org)
  • A team led by Jennifer Doudna, biochemist and leading authority on the CRISPR/Cas9 complex, showed how the Cas9 enzyme can work with short DNA sequences known as "PAM," for protospacer adjacent motif, to identify and bind with specific site of single-stranded RNA (ssRNA). (eurekalert.org)
  • Cas9 - Cas stands for CRISPR-assisted - is an RNA-guided enzyme that handles the sniping of DNA strands at the specified sequence site. (eurekalert.org)
  • CRISPR technology comprises a growing family of tools that can manipulate genes and their expression, including by targeting DNA with the enzymes Cas9 and Cas12 and targeting RNA with the enzyme Cas13. (eurekalert.org)
  • Zhang and his team, including first co-authors Omar Abudayyeh and Jonathan Gootenberg (both now McGovern Fellows), made use of a deactivated Cas13 to guide RESCUE to targeted cytosine bases on RNA transcripts, and used a novel, evolved, programmable enzyme to convert unwanted cytosine into uridine -- thereby directing a change in the RNA instructions. (eurekalert.org)
  • To address these questions, the researchers packaged a mouse Mecp2 RNA guide and human editing enzyme "editase" in a viral vector and introduced it directly into the hippocampus, the brain structure associated with learning and memory. (genengnews.com)
  • Deletion of the RNA-editing enzyme Apobec-1 in this model drastically reduces the number of polyps in the intestine. (asbmb.org)
  • Because production of the RNA deamination enzyme is induced by an inflammatory response, the researchers propose that editing of the mRNA of NEIL1 may be a way that cells provide themselves with a broader range of DNA repair in response to the oxidative stress of inflammation. (acs.org)
  • The conventional CRISPR-Cas9 system comprises two parts: the Cas9 enzyme, which acts like a wrench, and specific RNA guides (CRISPRs), which act as different socket heads. (innovations-report.com)
  • The RNA guides the Cas9 enzyme to the desired spot, where it cuts the DNA. (innovations-report.com)
  • An extension of the approach can switch off the molecular scissors even faster by addition of a second, chemically modified RNA drug that directs inactivation of the gene encoding the Cas9 enzyme. (innovations-report.com)
  • The REPAIR system is based on Cas13, an enzyme that does the same, but for RNA. (fiercebiotech.com)
  • The scientists created a deactivated version of the Cas13 enzyme, PspCas13b, which binds precisely to a stretch of RNA, but does not cut it. (fiercebiotech.com)
  • They combined the enzyme with the protein ADAR2, which switches A to I in RNA transcripts, and then improved the tool to cut down on off-target effects. (fiercebiotech.com)
  • The most widely used cytosine base editors (CBEs) induce deamination of DNA cytosines using the rat APOBEC1 enzyme, which is targeted by a linked Cas protein-guide RNA complex 3,4 . (massgeneral.org)
  • show that the in vivo targets of the principal editing enzyme, ADAR1, are long double-stranded RNA (dsRNA) structures in noncoding portions of cellular mRNAs. (sciencemag.org)
  • The CRISPR enzyme Cas13 (pink), part of the RESCUE platform, uses a special guide (red) to target RNAs (blue) in the cell. (fiercebiotech.com)
  • CRISPR editing of DNA uses the enzyme Cas9 to snip DNA at specific locations. (fiercebiotech.com)
  • Zhang's team used a deactivated form of a different enzyme, Cas13, to target RNA. (fiercebiotech.com)
  • Using a programmable enzyme, Zhang's team converted pathogenic cytosine into uridine, which in turn changed the instructions RNA provided for, say, protein synthesis. (fiercebiotech.com)
  • March 12, 2021 -- Researchers have discovered that an isoform of the RNA editing enzyme adenosine deaminase acting on RNA 1 (ADAR1) is responsible for regulating genome stability of telomeres at chromosomal ends. (scienceboard.net)
  • Human Z-RNA editing enzyme complexed with Z-RNA (Z-ribonucleic acid). (sciencephoto.com)
  • Computer model showing the structure of the human Zalpha domain of the RNA-editing enzyme ADAR1 (brown-orange, blue-purple) complexed with a synthetic Z-RNA (blue-green, yellow). (sciencephoto.com)
  • Interestingly, IFN-α induces gene expression of the RNA editing enzyme ADAR1-1 (ADAR1a-p150) and alters overall RNA editing activity. (springer.com)
  • A study in Nature Communications finds that an enzyme that edits RNA may loosen the genome's control over invasive snippets of DNA that affect how genes are expressed. (healthcanal.com)
  • In the new paper, scientists show that an enzyme called ADAR, which edits RNA in humans, flies, and many other creatures, edits double-stranded RNAs. (healthcanal.com)
  • found that the RNA-editing enzyme ADAR supports the activity of FAK. (sciencemag.org)
  • We found that CREB regulates ADAR1, an enzyme involved in RNA editing," said Bar-Eli, whose study findings appear in this month's issue of Nature Cell Biology . (healthcanal.com)
  • RNA editing by adenosine deamination is catalyzed by members of an enzyme family known as a denosine d e a minases that act on R NA (ADARs) ( 6 ). (pubmedcentralcanada.ca)
  • Additionally, the expression of RNA editing enzyme (ADAR1) was also upregulated in cancerous tissues compared to normal mucosa, and positively correlated with AZIN1 editing levels. (aacrjournals.org)
  • Herein we show that the adenosine-toinosine editing enzyme ADAR1 undergoes gene amplification in non-small cancer cell lines and primary tumors in association with higher levels of the corresponding mRNA and protein. (csic.es)
  • This invention relates generally to the production of proteins via genetic engineering techniques, and more specifically relates to the cloning and use of a novel RNA editing enzyme. (google.com)
  • RNA editing in Trypanosoma brucei mitochondria produces mature mRNAs by a series of enzyme-catalyzed reactions that specifically insert or delete uridylates in association with a macromolecular complex. (asm.org)
  • The process requires the Cas9 enzyme and guide RNA (gRNA), which directs Cas9 to the target DNA location. (idtdna.com)
  • We will do this by analyzing altered RNA processing in mouse brain deficient for the editing enzyme. (neurodegenerationresearch.eu)
  • 2004) Liver disintegration in the mouse embryo caused by deficiency in the RNA-editing enzyme ADAR1. (oalib.com)
  • Used to cut through a double strand of DNA in order to introduce genetic changes, CRISPR-Cas RNA-guided nucleases combine a bacterial gene-cutting enzyme called Cas9 with a short RNA segment that matches and binds to the target DNA sequence. (rna-seqblog.com)
  • The most common type of RNA editing is A-to-I editing by double-stranded RNA-specific adenosine deaminase (ADAR) enzymes. (nature.com)
  • Fig. 1: A-to-I RNA editing is catalysed by ADAR enzymes and is the most common type of RNA editing in Metazoa. (nature.com)
  • Nishikura, K. Functions and regulation of RNA editing by ADAR deaminases. (nature.com)
  • Functions and regulation of RNA editing by ADAR deaminases. (icr.org)
  • This RNA "editing" is mediated by adenosine deaminase acting on RNA (ADAR) enzymes. (sciencemag.org)
  • Specificity of our profiling was supported by observations of enrichment with known features of targets of adenosine deaminases acting on RNA (ADAR) and validation by means of capillary sequencing. (sciencemag.org)
  • Deamination is brought about by the action of specific editing enzymes, termed ADAR (adenosine deaminase acting on RNA). (springer.com)
  • The study was focused on fruit flies, ADAR, and the double-stranded RNA of the Hoppel transposon, but the ability of RNA editors to loosen the silencing of at least some transposons may be a source of individual variation in humans and other species too, said Brown University biologist Robert Reenan, senior author of the new study published online. (healthcanal.com)
  • Editing of double-stranded RNA - or a lack of editing - has already been linked to diseases in people, including amyloid lateral sclerosis and, specifically in the case of ADAR, Aicardi-Goutières syndrome. (healthcanal.com)
  • ADAR in humans functions the same way it does in flies, and double-stranded RNAs are made in humans the same way," said Reenan, professor of biology in the Department of Molecular Biology, Cell Biology and Biochemistry. (healthcanal.com)
  • Many of Reenan's studies focus on ADAR's editing activity in the development of the nervous system, but this investigation began years ago when lead author and then graduate student Yiannis Savva happened to overexpress ADAR in fruit fly salivary gland cells. (healthcanal.com)
  • They deleted the double-stranded RNA from chromosome four and found that ADAR was no longer there. (healthcanal.com)
  • The SNAP-ADAR tool has been comprehensively characterized in terms of potency, efficiency, codon scope, duration of the effect, concurrent editing, editing of endogenous transcripts, off-target editing in the mRNA/gRNA duplex, global off-target editing. (europa.eu)
  • We found the SNAP-ADAR system to be very powerful, to enable efficient, editing at various codons and transcripts with sufficient potency and duration. (europa.eu)
  • The SNAP-ADAR tool is the most comprehensively studied tool today and achieves an excellent balance of editing efficiency and off-target effects due to its unique assembly strategy. (europa.eu)
  • In lung adenocarcinoma cells, ADAR bound to and edited FAK mRNA in a manner that improved its stability, thus increasing the abundance of FAK protein and enhancing the migration of these cells. (sciencemag.org)
  • We found that the RNA-editing protein ADAR (adenosine deaminase acting on double-stranded RNA) acted as a facilitator of lung adenocarcinoma (LUAD) progression through its ability to stabilize transcripts encoding focal adhesion kinase (FAK). (sciencemag.org)
  • Molecular analyses revealed that ADAR posttranscriptionally increased FAK protein abundance by binding to the FAK transcript and editing a specific intronic site that resulted in the increased stabilization of FAK mRNA. (sciencemag.org)
  • Owing to the role of interferon in defense against microbial infection, the p150 isoform of Adar has been thought to function in the editing of double stranded viral RNA. (biomedcentral.com)
  • Adenosine deamination by adenosine deaminases that act on RNA (ADAR) seemingly only affects metazoan nuclear encoded RNAs. (frontiersin.org)
  • Axiomer® technology Editing Oligonucleotides (EONs) recruit endogenous ADAR to make single nucleotide changes to RNA in a highly specific and targeted manner. (pharmiweb.com)
  • PRQR ), today announced that a presentation titled "Axiomer® Technology: Therapeutic Oligonucleotides for Directing Site-Specific A-to-I Editing by Endogenous ADAR Enzymes" will be presented during the Oligonucleotide Therapeutics Society (OTS) Meeting to be held September 24-27, 2017 in Bordeaux, France. (pharmiweb.com)
  • The presentation is titled "Axiomer® Technology: Therapeutic Oligonucleotides for Directing Site-Specific A-to-I Editing by Endogenous ADAR Enzymes. (pharmiweb.com)
  • Gerard Platenburg, Chief Innovation Officer at ProQR added, "We are the first to show evidence of RNA editing using endogenous ADAR enzymes in an in vivo model. (pharmiweb.com)
  • AZIN1 RNA modification was mediated by the p110 isoform of adenosine deaminase, RNA-specific (ADAR1), but not by other ADAR family members, and resulted in substitution of glycine for serine at residue 367 in the AZIN1 protein, which was predicted to induce a conformational switch. (aacrjournals.org)
  • Adenosine deaminases acting on RNA (ADAR) enzymes, ADAR1 and ADAR2, convert adenosines in double-stranded RNA structures into inosines by hydrolytic deamination. (ovid.com)
  • It became apparent that disrupted RNA editing or abnormal ADAR expression is associated with several diseases including cancer, neurological disorders, metabolic diseases, viral infections, and autoimmune disorders. (ovid.com)
  • The roles of the double stranded RNA specific ADAR (Adenosine DeAminase that act on RNA) family members (ADARs) and the altered gene specific editing patterns were investigated in clinical specimens, cell models and mice. (bmj.com)
  • In humans, the most frequent type of editing is the conversion of A to I, which is catalysed by the dsRNA specific ADAR family of RNA editing enzymes. (bmj.com)
  • The method reveals a considerable variation in hyper-editing levels across species, which is partly explained by differences in the potential of sequences to form dsRNA structures and the variability of ADAR proteins. (biomedcentral.com)
  • It is catalyzed by the family of adenosine deaminases acting on RNA (ADAR) enzymes [ 3 ] and is considered to be more active in the brain [ 4 ]. (biomedcentral.com)
  • Collectively, these studies emphasize the importance of ADAR-mediated RNA editing to development, aging, and tissue homeostasis. (biomedcentral.com)
  • We analyzed RNA editing at codon-altering sites using in situ sequencing at single-cell resolution, in combination with the detection of individual ADAR enzymes and specific cell type marker transcripts. (biomedcentral.com)
  • We found increasing editing diversity throughout development, which arises through regional- and cell type-specific regulation of ADAR enzymes and target transcripts. (biomedcentral.com)
  • This schematic shows how RNA-guided Cas9 working with PAMmer can target ssRNA for programmable, sequence-specific cleavage. (eurekalert.org)
  • A team of researchers with Berkeley Lab and the University of California (UC) Berkeley has demonstrated a means by which the CRISPR/Cas9 protein complex can be programmed to recognize and cleave RNA at sequence-specific target sites. (eurekalert.org)
  • They are designating this RNA-targeting CRISPR/Cas9 complex as RCas9. (eurekalert.org)
  • Together, CRISPR and Cas9 can be used to precisely edit the DNA instructions in a targeted genome for making desired types of proteins. (eurekalert.org)
  • Just as Cas9 can be used to cut or bind DNA in a sequence-specific manner, RCas9 can cut or bind RNA in a sequence-specific manner," says Mitchell O'Connell, a member of Doudna's research group and the lead author of a paper in Nature that describes this research titled "Programmable RNA recognition and cleavage by CRISPR/Cas9. (eurekalert.org)
  • In an earlier study, Doudna and her group showed that the genome editing ability of Cas9 is made possible by presence of PAM, which marks where cutting is to commence and activates the enzyme's strand-cleaving activity. (eurekalert.org)
  • They used Cas9 enzymes from the bacterium Streptococcus pyogenes to perform a variety of in vitro cleavage experiments using a panel of RNA and DNA targets. (eurekalert.org)
  • In addition, some cell types, such as neurons, are difficult to edit using CRISPR/Cas9-mediated editing, and new strategies are needed to treat devastating diseases that affect the brain. (eurekalert.org)
  • Orthogonal Cas9 proteins for RNA-guided gene regulation and editing. (nih.gov)
  • The Cas9 protein from the Streptococcus pyogenes CRISPR-Cas acquired immune system has been adapted for both RNA-guided genome editing and gene regulation in a variety of organisms, but it can mediate only a single activity at a time within any given cell. (nih.gov)
  • Here we characterize a set of fully orthogonal Cas9 proteins and demonstrate their ability to mediate simultaneous and independently targeted gene regulation and editing in bacteria and in human cells. (nih.gov)
  • CRISPR/Cas9 gene editing activity runs continuously, though, leading to risk of additional editing at unwanted sites. (innovations-report.com)
  • Now, researchers at University of California, San Diego School of Medicine, Ludwig Cancer Research and Isis Pharmaceuticals demonstrate a commercially feasible way to use RNA to turn the CRISPR-Cas9 system on and off as desired -- permanently editing a gene, but only temporarily activating CRISPR-Cas9. (innovations-report.com)
  • These RNAs guide the Cas9 protein to the target gene on a DNA strand. (innovations-report.com)
  • CRISPR/Cas9 works like this: researchers design a "guide" RNA to match the sequence of a specific target gene. (innovations-report.com)
  • The new approach introduces chemically modified, RNA-based drugs to transiently activate the CRISPR/Cas9 gene editing system. (innovations-report.com)
  • The RNA-based drugs we developed in this study provide many advantages over the current CRISPR/Cas9 system, such as increased editing efficiency and potential selectivity," said Cleveland. (innovations-report.com)
  • To create such a tool, the endogenous CRISPR pathway was reduced to two principal components: the Cas9 nuclease and a guide RNA (gRNA) 1-7 . (sigmaaldrich.com)
  • CRISPR-Cas9 gene editing has proved useful in blocking specific genes to correct mutations, but it makes permanent changes to the genome. (fiercebiotech.com)
  • Liu's work, published in Nature , uses a guide RNA and catalytically impaired CRISPR-Cas9 to convert A-T base pairs to G-C base pairs in the genome, enabling the editing of single point mutations without the induction of double-stranded DNA breaks (DSBs). (genomeweb.com)
  • They also tested the off-target activity of the ABEs and observed off-target base editing at only four of 12 known Cas9 off-target sites (33 percent) as compared to detectable modifications by Cas9 nuclease at nine of the 12 known off-target loci (75 percent). (genomeweb.com)
  • Several other research groups are working on RNA-editing technologies, including a team at the University of California, San Diego (UCSD), which used an RNA-targeted Cas9 system in lab models of myotonic dystrophy two years ago. (fiercebiotech.com)
  • Here, we report that RNA-guided Cas9 nuclease efficiently facilitates genome editing in both mammalian cells and zebrafish embryos in a simple and robust manner. (nih.gov)
  • A two plasmid system for editing bacterial genomes using an RNA-guided Cas9 nuclease. (addgene.org)
  • Target-specific cytoplasmic and nuclear knockdown in host gene expression using ZIF-C is shown for the first time through RNAi and CRISPR/Cas9 based gene editing in PC cells. (rsc.org)
  • LA JOLLA-Most people have heard of the CRISPR/Cas9 gene-editing technology, which acts as targeted molecular scissors to cut and replace disease-causing genes with healthy ones. (salk.edu)
  • CRISPRs are bacterial immune systems that contain many defense enzymes such as the Cas9 "molecular scissors," which scientists including Hsu have engineered as a powerful DNA-targeting gene-editing tool. (salk.edu)
  • If you are looking to optimize the important step of delivering RNA to your cells for the purpose of CRISPR-Cas9 gene editing or RNAi, check out the DharmaFECT transfection reagent portfolio! (horizondiscovery.com)
  • RGENs consist of three components: Cas9 endonuclease, CRISPR RNA (crRNA) that complementarily binds to the target site of the genomic DNA, and trans -activating CRISPR RNA (tracrRNA). (g3journal.org)
  • DNA vectors expressing maize codon-optimized Streptococcus pyogenes Cas9 endonuclease and single guide RNAs were cointroduced with or without DNA repair templates into maize immature embryos by biolistic transformation targeting five different genomic regions: upstream of the liguleless1 ( LIG1 ) gene, male fertility genes ( Ms26 and Ms45 ), and acetolactate synthase (ALS) genes ( ALS1 and ALS2 ). (plantphysiol.org)
  • Biolistic delivery of guide RNAs (as RNA molecules) directly into immature embryo cells containing preintegrated Cas9 also resulted in targeted mutations. (plantphysiol.org)
  • Double-strand breaks generated by RNA-guided Cas9 endonuclease also stimulated insertion of a trait gene at a site near LIG1 by homology-directed repair. (plantphysiol.org)
  • The examples reported in this study demonstrate the utility of Cas9-guide RNA technology as a plant genome editing tool to enhance plant breeding and crop research needed to meet growing agriculture demands of the future. (plantphysiol.org)
  • Genome editing using standard tools (ZFN, TALEN, and CRISPR/Cas9) rely on double strand breaks to edit the genome. (g3journal.org)
  • Under the direction of a guide RNA (gRNA), the Cas9 nuclease binds to an opened DNA strand that pairs with the gRNA and induces a double-strand break (DSB). (g3journal.org)
  • Use of CRISPR-Cas9 has revolutionized targeted genome editing. (idtdna.com)
  • The Alt-R™ CRISPR-Cas9 System provides custom CRISPR crRNA and a universal CRISPR tracrRNA, both of which are required for CRISPR-Cas9 genome editing using the Alt-R CRISPR-Cas9 System protocol. (idtdna.com)
  • Can I use the Edit-R synthetic RNA components with my own Cas9 nuclease mRNA? (horizondiscovery.com)
  • We have validated the use of Edit-R synthetic tracrRNA and crRNAs and achieved efficient gene editing utilizing the Edit-R Cas9 expression plasmids in mammalian cell lines. (horizondiscovery.com)
  • Additionally, you must be able to efficiently co-transfect your Cas9 mRNA or plasmid DNA with the synthetic RNAs. (horizondiscovery.com)
  • To this end, we engineered a nuclease-deficient CRISPR/Cas9 system as a recruitment platform for non-nuclease DNA/RNA editing enzymes that catalyze C·G→T·A conversions by cytidine deamination. (rutgers.edu)
  • The Cas9 nuclease is directed to DNA using a guide RNA (gRNA), either as the native dual-RNA system consisting of a DNA-targeting CRISPR RNA (crRNA) and trans-activating crRNA (tracrRNA), or a chimeric single guide RNA (sgRNA) created through the fusion of crRNA and tracrRNA. (technologynetworks.com)
  • These modified RNAs were co-delivered into cells with Cas9 mRNA or Cas9 protein using electroporation. (technologynetworks.com)
  • Some modification patterns were found to significantly improve CRISPR-Cas9 gene editing when used with Cas9 mRNA compared to the unmodified versions, yet most modifications did not significantly increase gene editing when used with Cas9 protein. (technologynetworks.com)
  • Transfection reagent-mediated delivery of these modified gRNAs into a Cas9-expressing cell line resulted in similar editing efficiencies as the unmodified synthetic gRNAs, and cellular toxicity was observed with certain modification patterns. (technologynetworks.com)
  • Of the modifications that were nontoxic, some patterns showed modest improvement in editing efficiency when co-transfected with Cas9 mRNA or Cas9 protein. (technologynetworks.com)
  • Overall, our results indicate that MS modifications are required for experiments with co-electroporation of Cas9 mRNA and synthetic gRNA, yet have no impact on editing efficiency when delivered with lipid-based transfection reagents. (technologynetworks.com)
  • To demonstrate this, the team showed that in human cells, RESCUE can target specific sites in the RNA encoding β-catenin, that are known to be phosphorylated on the protein product, leading to a temporary increase in β-catenin activation and cell growth. (eurekalert.org)
  • The technology recoded enough RNA to restore half of the normal protein in three different kinds of neurons in the Rett mouse, demonstrating that programmable RNA editing can be utilized to repair mutations in mouse models of neurological disease. (genengnews.com)
  • The research is published in Cell Reports in a paper titled, " In Vivo Repair of a Protein Underlying a Neurological Disorder by Programmable RNA Editing . (genengnews.com)
  • The idea behind the strategy used in this new study is to produce a healthy MeCP2 protein by repairing the genetic error in the RNA. (genengnews.com)
  • Does editing restore MeCP2 protein function? (genengnews.com)
  • The injected editase repaired about half of the RNA produced by the mutant MeCP2 gene in each of three types of neurons located in different regions of the hippocampus and MeCP2 protein function was equally repaired in the neurons. (genengnews.com)
  • The 57,000 recoding sites they found in the squid brain (as compared with 100 known recoding sites in humans and 600 in the fruit fly) created tremendous protein diversity, suggesting an important role for RNA editing in the brain physiology of the squid. (mbl.edu)
  • Recent transcriptomic studies have identified a number of 'recoding' sites at which A-to-I editing results in non-synonymous substitutions in protein-coding sequences. (nature.com)
  • Fig. 3: Editing can modify protein function, generate new protein products, alter gene regulation and provide immune protection against endogenous dsRNAs. (nature.com)
  • New protein-RNA structures illuminate substrate recognition by the RNA editing ADARs. (nature.com)
  • Furthermore, RNA editing in the 3'-untranslated region has been shown to be the alteration that most frequently leads to changes in RNA stability, RNA localization and protein translation. (asbmb.org)
  • Other researchers later discovered that the Apobec-1 biochemical function requires a cofactor, and two different essential cofactors were discovered - Apobec-1 complementation factor, or A1cf, and RNA binding motif protein 47, or Rbm47. (asbmb.org)
  • RNA-editing alterations also have been reported in cancers and neurological disorders, and Davidson's lab is pursuing the profiling of DNA, RNA and protein levels in cancer tissues to substantiate further the diagnostic potential of RNA editing. (asbmb.org)
  • RNA-editing reactions can alter nucleotides and change the protein-coding properties of RNA molecules, and they are known to alter the function of some nervous system proteins. (acs.org)
  • Scientists initially thought that the information coded into RNAs didn't change-it was either used to make a protein, or the RNAs were used directly for some specific purpose in the cell. (icr.org)
  • All major animal groups from jellyfish to humans use amazing cellular machinery to modify RNA transcribed from both protein-coding and non-coding RNA genes. (icr.org)
  • 2 Thus, a single gene can produce a wide array of RNA variants, including many different protein forms if the RNAs are translated (made into proteins). (icr.org)
  • CBE-induced RNA edits occur in both protein-coding and non-protein-coding sequences and generate missense, nonsense, splice site, and 5' and 3' untranslated region mutations. (massgeneral.org)
  • RNA editing in mRNAs effectively alters the amino acid sequence of the encoded protein so that it differs from that predicted by the genomic DNA sequence. (wikipedia.org)
  • ADAR1p150 is mostly active in the cytoplasm where it regulates dsRNA-sensing mechanisms and editing the 3'-untranslated region (3'-UTR) dsRNAs to suppress activation of melanoma-differentiation-associated protein 5, mitochondrial antiviral signaling protein, and interferon (MDA5-MAVS-IFN) signaling. (scienceboard.net)
  • Then, exploiting the replication protein A 32 kDa subunit (RPA32) as a marker for R-loops, the researchers showed that ADAR1 depletion resulted in significantly increased formation of the RNA-DNA hybrids, specifically in telomeric repeat regions. (scienceboard.net)
  • Furthermore, editing of noncoding sequences, like microRNAs, can regulate protein expression, while editing of Alu sequences can affect translational efficiency and editing of proximal sequences. (mdpi.com)
  • We also implemented RNA editing for the inclusion N- and C-terminal protein localization signals and achieved photocontrol over protein localization. (europa.eu)
  • Editing of the mRNA that encodes actin crosslinking protein Filamin A (FLNA) mediates a Q-to-R transition in the interactive C-terminal region. (medworm.com)
  • RIP1 is a dual-targeted protein that selectively interacts with PPR editing factors and affects 14 editing events in chloroplasts and over 400 editing events in mitochondria. (cornell.edu)
  • RIP1 belongs to a small protein family, 5 members of which were later shown to be major editing factors. (cornell.edu)
  • Homology searching with the RIP protein led to the discovery of ORRM1, a hybrid protein which possesses a RIP-like domain at its N terminus and an RNA Recognition Motif (RRM) domain at its C terminus. (cornell.edu)
  • Loss of this protein leads to editing defects at many plastid sites, most of which are also controlled by ORRM1. (cornell.edu)
  • Furthermore, RNA editing is potentially implicated in new start or stop codon generation, and may affect alternative splicing of certain protein-coding transcripts. (biomedcentral.com)
  • However, a global vision of RNA editing in plant nuclear protein-coding transcripts has not been realized. (biomedcentral.com)
  • In contrast to the traditional dogma of DNA makes RNA makes protein, RNA-editing is a non-heritable change to the RNA, which can result in both increased diversity of the transcriptional repertoire, and of the resulting peptide products. (biomedcentral.com)
  • Editing in coding regions of mRNAs can therefore lead to a codon exchange and the subsequent translation of a protein that differs from the genomically encoded version. (frontiersin.org)
  • There are perhaps a few dozen known RNA editing sites that affect protein sequence, though more presumably exist (incidentally, many of these were found by Billy Li, one of the authors of the Lin/Piskol et al. (genomesunzipped.org)
  • Now, Salk Institute scientists have created a new tool that targets not DNA, but RNA, and used it to correct a protein imbalance in cells from a dementia patient, restoring them to healthy levels. (salk.edu)
  • The team genetically engineered CasRx to target RNA sequences for the version of the tau protein that is overabundant. (salk.edu)
  • The Salk team is excited about the possibilities their tool opens up for exploring new biological questions about RNA and protein function, as well as therapies to tackle RNA and protein-based diseases. (salk.edu)
  • We find that the residues encoded by edited codons are significantly biased toward involvement in helices and protein structural cores. (cam.ac.uk)
  • The puzzling point of the finding is that the editing occurs on mRNA and protein 3D structures cannot play roles in the editing processes. (cam.ac.uk)
  • REMSA was performed with affinity-purified 6xHis-tagged ORRM6 protein and fluorescently labeled synthetic accD -C794, psbF -C77, and psbE -C214 RNAs (below). (plantphysiol.org)
  • expression of edited AZIN1 increased cell proliferation, anchorage-independent growth, and invasion and augmented tumor incidence in mice, supporting a protumorigenic function for this edited protein. (aacrjournals.org)
  • Mechanistically, edited AZIN1 exhibited increased binding affinity for antizyme, a tumor suppressor that inhibits proliferation, and enhanced protein stability compared with wild-type AZIN1. (aacrjournals.org)
  • These results establish liver-specific RNA editing of AZIN1 as an oncogenic event that modulates AZIN1 protein function and drives tumor initiation and progression in HCC. (aacrjournals.org)
  • For each tissue-location, 8-16% of the predicted editing sites were known from the DARNED database, 22-32% of the editing sites were located within protein coding genes, and 70% of the editing sites occur within noncoding RNAs. (arvojournals.org)
  • In addition, 30 editing sites were found within age-related macular degeneration GWAS loci with 5 of them in 3' UTR of protein coding genes. (arvojournals.org)
  • SNPs within these editing sites, especially if located within protein coding regions, could be contributory to disease and deserve more attention when we try to understand the genetic architecture of disease. (arvojournals.org)
  • Due to the differentially expressed ADAR1 and ADAR2 in tumours, the altered gene specific editing activities, which was reflected by the hyper-editing of FLNB (filamin B, β) and the hypo-editing of COPA (coatomer protein complex, subunit α), are closely associated with HCC pathogenesis. (bmj.com)
  • Using a mitochondrial fraction enriched for in vitro RNA editing activity, we produced several monoclonal antibodies that are specific for a 21-kDa guide RNA (gRNA) binding protein initially identified by UV cross-linking. (asm.org)
  • These studies indicate that the 21-kDa protein associates with the ribonucleoprotein complex (or complexes) that catalyze RNA editing. (asm.org)
  • The chapters span the editing of protein coding mRNAs, small regulatory RNAs, tRNAs and non-coding sequences. (caister.com)
  • This chapter focuses on how RNA editing affects protein function and higher order physiology. (caister.com)
  • A code describing how PPR proteins recognise their RNA targets promises to accelerate research on these proteins, but making use of this code requires accurate definition and annotation of all of the various nucleotide-binding motifs in each protein. (ovid.com)
  • MicroRNAs (miRNAs) are short (around 20-22 nucleotides) RNAs that post-transcriptionally regulate gene expression by base-pairing with complementary sequences in the 3' untranslated regions (UTRs) of protein-coding transcripts and directing translational repression or transcript degradation [ 1 - 5 ]. (biomedcentral.com)
  • The technology recoded enough RNA to restore half of the normal protein in three different kinds of neurons in the Rett mouse. (technologynetworks.com)
  • The instructions for the protein it makes are coded in a unique combination of four genomic "letters" - A, C, G and T. The cell transcribes the DNA code into RNA and then into protein. (technologynetworks.com)
  • Editing in the coding region of a transcript can lead to an amino acid substitution (recoding), resulting in a novel protein isoform and, possibly, an altered protein function. (biomedcentral.com)
  • In this paper, we investigated 82 protein-coding genes in the chloroplast genome of G. biloba and identified 255 editing sites, which is the highest number of RNA editing events reported in a gymnosperm. (biomedcentral.com)
  • Most of the RNA editing sites can restore amino acid conservation, increase hydrophobicity, and even influence protein structures. (biomedcentral.com)
  • In higher plants, RNA editing mainly occurs in the protein-encoding genes of mitochondria and chloroplasts and it mostly converts C to U, although hornwort and fern have abundant U to C editing. (biomedcentral.com)
  • The alternative splicing, as a result of editing, leads to a frameshift and decreased ADAR2 protein levels. (biomedcentral.com)
  • Anti-RNA-editing complex protein MP81 antibody is a Single domain antibody that binds to an RNA-editing complex protein MP81. (creativebiolabs.net)
  • Trypanosome RNA editing utilizes a seven polypeptide complex that includes two RNA ligases, band IV and band V. We now find that band IV protein contributes to the structural stability of the editing complex, so its lethal genetic knock‐out could reflect structural or catalytic requirements. (embopress.org)
  • To assess the catalytic role in editing, we generated cell lines which inducibly replaced band IV protein with an enzymatically inactive but structurally conserved version. (embopress.org)
  • Base editing was conducted in rabbit zygotes by microinjection of BE3-encoding mRNA and single guide RNAs (sgRNAs). (nature.com)
  • in some cases the majority of nucleotides in an mRNA sequence may result from editing. (wikipedia.org)
  • Most of the RNA modifications are found on transfer-RNA and ribosomal-RNA, but also eukaryotic mRNA has been shown to be modified with multiple different modifications. (wikipedia.org)
  • Certain modifications like 2'O-methylated nucleotides has been associated with cells ability to distinguish own mRNA from foreign RNA. (wikipedia.org)
  • Editing of the pre-mRNA results in conversion to Arg (CGG) being encoded at this position. (wikipedia.org)
  • Deficiency of vitamin B1 is correlated with alterations in editing of Glur2 pre-mRNA. (wikipedia.org)
  • We found ways to suppress off-target editing in the mRNA/gRNA duplex by optimizing the chemistry of the guideRNA. (europa.eu)
  • RNA editing was discovered in an mRNA encoded by the kinetoplastid mitochondria of trypanosomes ( 3 ), and at first most scientists believed the phenomenon would be limited to these unusual protozoa. (pubmedcentralcanada.ca)
  • However, only a year later the first example of RNA editing in a mammal, in a nuclear-encoded mRNA, was reported ( 4 ). (pubmedcentralcanada.ca)
  • Here, we carried out an extensive search for potential editing sites in nuclear transcripts utilizing mRNA MPSS and PARE data. (biomedcentral.com)
  • Thus, also editing in non-translated regions of an mRNA may have profound impact on the fate of the affected RNA. (frontiersin.org)
  • In May of last year, Li and colleagues reported that they had observed over 10,000 sequence mismatches between messenger RNA (mRNA) and DNA from the same individuals (RDD sites, for RNA-DNA differences) [1]. (genomesunzipped.org)
  • The immunoprecipitated material also contains gRNA-specific endoribonuclease, terminal uridylyltransferase, and RNA ligase activities as well as gRNA and both edited and unedited mRNA. (asm.org)
  • The edited mRNA sequence is specified by trans -acting small RNA molecules called gRNAs, which are complementary to their edited cognate mRNAs ( 4 ). (asm.org)
  • A 5- to 15-nucleotide (nt) region at the 5′ end of gRNAs is complementary to the sequence of its cognate preedited mRNA that is immediately 3′ to the region that will be edited. (asm.org)
  • A tripartite motif located in the centre of the 7.5kb exon 26 of apolipoprotein B (apoB) mRNA directs editosome assembly and site-specific cytidine-to-uridine editing at nucleotide 6666. (biochemj.org)
  • apoB mRNA editing is a post-transcriptional event, occurring primarily at the time exon 26 is spliced or at a time after splicing, but before nuclear export. (biochemj.org)
  • The results suggested that commitment of pre-mRNA to the splicing and/or nuclear-export pathways may play a role in regulating editing-site utilization. (biochemj.org)
  • Englander MT, Dulawa SC, Bhansali P, Schmauss C (2005) How stress and fluoxetine modulate serotonin 2C receptor pre-mRNA editing. (oalib.com)
  • Interestingly, rodent ADAR2 edits its own pre-mRNA, creating an alternative splice site. (biomedcentral.com)
  • Several instances show that the genomic arginine codon CGG is edited in the mRNA to the tryptophan codon TGG in amino acid positions that are highly conserved as tryptophan in the homologous proteins of other species. (harvard.edu)
  • The first gRNA overlaps the 3′ end of the editing domain, so could anchor to the unedited mRNA forming a partial duplex. (embopress.org)
  • The editing site can be identified as the mismatch abutting the anchor duplex: a mismatched purine in the gRNA specifies U insertion, while a mismatched U in the pre‐mRNA specifies U‐deletion. (embopress.org)
  • Each editing cycle begins with endonuclease cleavage of the pre‐mRNA at the first mismatch adjacent to the anchor duplex. (embopress.org)
  • Finally, RNA ligase seals the pre‐mRNA. (embopress.org)
  • This allows the gRNA:pre‐mRNA duplex to zip up to the next mismatch where the next cycle of editing occurs. (embopress.org)
  • Kinetoplastid RNA (kRNA) editing is a process that creates translatable mitochondrial mRNA transcripts from cryptogene encoded RNAs and is unique for kinetoplastids, such as Trypanosoma brucei. (escholarship.org)
  • In vivo experiments indicate a role for MRB1590 in editing mitochondrial mRNA transcripts, in particular the transcript encoding the ATP synthase subunit 6 (A6). (escholarship.org)
  • ADAR1-directed editing of these cellular targets is critical to avoid activation of an immune response to dsRNA in the cytoplasm, because dsRNA is also a marker of viral infection. (sciencemag.org)
  • In addition to RNA editing, additional functions have been proposed for ADAR1. (sciencemag.org)
  • To determine the specific role of RNA editing by ADAR1, we generated mice with an editing-deficient knock-in mutation ( Adar1 E861A , where E861A denotes Glu 861 →Ala 861 ). (sciencemag.org)
  • Adar1 E861A/E861A embryos died at ~E13.5 (embryonic day 13.5), with activated interferon and double-stranded RNA (dsRNA)-sensing pathways. (sciencemag.org)
  • A-to-I editing of endogenous dsRNA is the essential function of ADAR1, preventing the activation of the cytosolic dsRNA response by endogenous transcripts. (sciencemag.org)
  • This underscores the importance of ADAR1-mediated A-to-I editing activity in the maintenance of telomere stability. (scienceboard.net)
  • The researchers found that ADAR1 depletion resulted in the accumulation of RNA and DNA strands of RNA-DNA hybrids of canonical and variant telomere repeats associated with those that are found in cancer cells. (scienceboard.net)
  • Besides editing, ADAR1 also interacts with other dsRNA-binding proteins in editing-independent manners. (mdpi.com)
  • Elucidating the disease-specific patterns of editing and/or ADAR1 expression may be useful in making diagnoses and prognoses. (mdpi.com)
  • Bar-Eli's team evaluated the RNA editing functioning of ADAR1 in microRNAs (miRNAs). (healthcanal.com)
  • RNA editing occurs only in the non-metastatic (ADAR1-positive), but not in the metastatic melanoma cells (ADAR1-negative). (healthcanal.com)
  • ADAR1-mediated editing of messenger RNA may be an important mechanism in multiple myeloma pathogenesis. (mdedge.com)
  • ADAR1-mediated editing of NEIL1 leads to a weakened DNA base excision repair mechanism. (mdedge.com)
  • From a functional perspective, ADAR1 overexpression enhances the editing frequencies of target transcripts such as NEIL1 and miR-381. (csic.es)
  • Overall, our results indicate a role for ADAR1 as a lung cancer oncogene undergoing gene amplification-associated activation that affects downstream RNA editing patterns and patient prognosis. (csic.es)
  • ADAR1 isoforms are adenosine deaminases that edit and destabilize double-stranded RNA reducing its immunostimulatory activities. (elifesciences.org)
  • ADAR1 alters the RNA coding sequence, because I is read as G, and it also destabilizes dsRNA because A:U base pairs are disrupted than I:U mismatches. (elifesciences.org)
  • We show that ADAR1, but not ADAR2, takes part in the editing of F11R however editing alone is not sufficient for obtaining an elevation in RNA levels. (oalib.com)
  • Wang Q, Khillan J, Gadue P, Nishikura K (2000) Requirement of the RNA editing deaminase ADAR1 gene for embryonic erythropoiesis. (oalib.com)
  • ADAR1 and ADAR2 have similar sequence features, including double-stranded RNA binding domains (dsRBDs) and a deaminase domain. (surrey.ac.uk)
  • Here we show that ADAR1-induced hyper-editing in normal human hematopoietic progenitors impairs miR-26a maturation, which represses CDKN1A expression indirectly via EZH2, thereby accelerating cell-cycle transit. (diagenode.com)
  • ADAR1 and ADAR2 have distinct yet overlapping specificities for editing substrates, resulting from how they are able to interact with specific adenosines while being constrained by the structure of the editing substrates [ 8 ]. (biomedcentral.com)
  • The probe is derived from the Z-DNA binding domain of the human double-stranded RNA adenosine deaminase 1 (ADAR1), named ZαADAR1. (ntu.edu.sg)
  • A powerful scientific tool for editing the DNA instructions in a genome can now also be applied to RNA, the molecule that translates DNA's genetic instructions into the production of proteins. (eurekalert.org)
  • Targeting disease-linked mutations in RNA, which is relatively short-lived, would avoid making permanent changes to the genome. (eurekalert.org)
  • RNA editing is unique among these modifications because it not only alters the cellular fate of RNA molecules but also alters their sequence relative to the genome. (nature.com)
  • However, systematic mapping of the editome across the animal kingdom has revealed that most A-to-I editing sites are located within mobile elements in non-coding parts of the genome. (nature.com)
  • The discovery of the type II prokaryotic CRISPR "immune system" has allowed for the development for an RNA-guided genome editing tool that is simple, easy and quick to implement. (sigmaaldrich.com)
  • REPAIR can fix mutations without tampering with the genome, and because RNA naturally degrades, it's a potentially reversible fix," said co-first author David Cox, a graduate student in Zhang's lab. (fiercebiotech.com)
  • When the workings of the genome were first being discovered, the central evolutionary dogma of molecular biology claimed that genetic information passes consistently from DNA to RNA to proteins. (icr.org)
  • In an interview, lead researcher Dr. Eli Eisenberg stated, "We have demonstrated that RNA editing is a major player in genetic information processing rather than an exception to the rule" and "the squid's RNA editing dramatically reshaped its entire proteome-the entire set of proteins expressed by a genome, cell, tissue, or organism at a certain time. (icr.org)
  • NEW YORK (GenomeWeb) - Broad Institute researchers David Liu and Feng Zhang have both developed new CRISPR-based systems, one for editing point mutations in the genome and the other for editing RNA, they revealed today in separate studies. (genomeweb.com)
  • Recent advances with the type II clustered regularly interspaced short palindromic repeats (CRISPR) system promise an improved approach to genome editing. (nih.gov)
  • To date, a total of 13 edited genes have been identified within nonrepetitive regions of the human genome (table S1). (sciencemag.org)
  • Here, we report an efficient and unbiased genome-wide approach to identify RNA editing sites that uses tailored target capture followed by massively parallel DNA sequencing. (sciencemag.org)
  • In the last few years, massive transcriptome sequencing has been employed to identify putative RNA editing changes at genome scale. (frontiersin.org)
  • When researchers first reported 3 years ago that they had created base editors, a version of the powerful genome-editing tool CRISPR, excitement swirled around their distinct powers to more subtly alter DNA compared with CRISPR itself. (sott.net)
  • Jia Chen, who does genome editing research at ShanghaiTech University in China and was not involved in the new work, was not as surprised, noting that deaminases were originally described as having the ability to alter RNA. (sott.net)
  • Large-scale, genome-wide studies report that RNA binding proteins are altered in cancers, but it is unclear how these proteins control tumor progression. (sciencemag.org)
  • Some types of RNA editing repair or correct the information encoded by the genome, whereas others act to diversify this information, offering an organism the potential for greater complexity. (pubmedcentralcanada.ca)
  • For each RDD site with at least five reads mismatching the genome, we calculated the fraction of reads with the mismatch (or the match) at each position in the alignment of the RNA-seq read to the genome (on the + DNA strand). (genomesunzipped.org)
  • They argue that these two effects could lead to mapping biases, such that sequencing reads carrying an edited base will only map to the genome if the mismatch is at the end of the read. (genomesunzipped.org)
  • CRISPR has revolutionized genome engineering, and we wanted to expand the toolbox from DNA to RNA. (salk.edu)
  • Although editing of both RNA and DNA substrates has been known to occur for some time, the extent and implications of these modifications have been grossly underappreciated until recent genome-wide and disease-association studies were reported. (garvan.org.au)
  • Mitochondrial RNAs differ from the mitochondrial genome at over 1300 sites, and both coding (mRNAs) and non-coding RNAs (rRNAs and tRNAs) are affected. (caister.com)
  • Furthermore, genome-scale analysis showed that 96.5% of B. mori genes have one or more targetable sites that can be edited by BE3 for inactivation, with a median of 11 sites per gene. (g3journal.org)
  • The clustered regularly interspaced short palindromic repeat (CRISPR) system has been widely used for site-specific genome editing in various organisms and cell lines ( Sander and Joung 2014 ). (g3journal.org)
  • Thus, approaches to precisely edit the genome while avoiding DSBs are needed. (g3journal.org)
  • Several modified systems have been developed to overcome the drawbacks of DSB-based genome editing. (g3journal.org)
  • For a further six miRNAs, we identified A-to-I editing of transcripts derived from the opposite strand of the genome to the annotated miRNA. (biomedcentral.com)
  • The inventors have constructed conjugative plasmids for intra- and inter-species delivery and expression of RNA-guided CRISPR-Cas transposases for organism- and site-specific genome editing by targeted transposon insertion. (universityofcalifornia.edu)
  • genome editing in strains in which homologous recombination or other repair-based editing is not feasible. (universityofcalifornia.edu)
  • The conversion of U to C was also found in addition of C to U. However, no editing was expected through out the entire transcripts of chloroplast genome from Psilotum. (nii.ac.jp)
  • Phylogenetic relationship based in the nucleotide sequence of chloroplast genome was not altered even when the nucleotide sequence was collected by RNA editing. (nii.ac.jp)
  • What reagents will I need in addition to the Alt-R™ RNAs to do a CRISPR genome editing experiment? (idtdna.com)
  • The degree to which the transcriptome of a given species undergoes hyper-editing is governed by the repertoire of repeats in the underlying genome. (biomedcentral.com)
  • Strikingly, the vast majority of editing sites found to date occur in non-coding regions of the genome. (biomedcentral.com)
  • Description Nuclease-dependent precise genome editing such as correction of point mutations requires introduction of targeted DNA double strand breaks (DSB) and activation of homology dependent repair (HDR), limiting its application to proliferating cells. (rutgers.edu)
  • The G. biloba chloroplast genome possesses the highest number of RNA editing events reported so far in a seed plant. (biomedcentral.com)
  • Harvard Medical School investigators at Massachusetts General Hospital have developed a method for detecting unwanted DNA breaks-across the entire genome of human cells-induced by the popular gene-editing tools called CRISPR-Cas RNA-guided nucleases (RGNs). (rna-seqblog.com)
  • In addition, GUIDE-seq was able to verify that their approach for improving the accuracy of CRISPR-Cas by shortening the guiding RNA segment reduced the number of double-strand breaks throughout the genome. (rna-seqblog.com)
  • The researchers reported that RNA of genes other than Mecp2 also were inadvertently edited, known as off-target effects. (genengnews.com)
  • Copies of programs in the DNA, called genes , are transcribed into RNA much like programs from a computer hard drive are copied into temporary memory so the software can be readily used. (icr.org)
  • In fact, they found over 500,000 sites in coral genes where the sequence had been altered with RNA editing. (icr.org)
  • RNA, as everyone knows, helps change genes into proteins that can be utilized. (i4u.com)
  • Here we show that a CBE with rat APOBEC1 can cause extensive transcriptome-wide deamination of RNA cytosines in human cells, inducing tens of thousands of C-to-U edits with frequencies ranging from 0.07% to 100% in 38-58% of expressed genes. (massgeneral.org)
  • Despite previous thoughts, large-scale projects like ENCODE have clearly demonstrated that more than 80% of mammalian genomes is transcribed and comprises numerous genes for non-coding RNAs ( Consortium, 2012 ). (frontiersin.org)
  • The biological functions of edited mi RNAs are different from unedited forms, as they recognize a different set of genes. (healthcanal.com)
  • To date, no systemic study on RNA editing of plant nuclear genes has been reported. (biomedcentral.com)
  • Interestingly, a sizable portion of these nuclear genes are involved in chloroplast- or mitochondrion-related functions, and many editing events are tissue-specific. (biomedcentral.com)
  • The results indicate that RNA editing is an essential RNA-based regulatory layer not only for mitochondrial and chloroplast genes but also for nuclear genes. (biomedcentral.com)
  • In humans, double stranded RNA structures often form in the long 3' UTR regions of genes when juxtaposed Alu repeat elements are present. (biomedcentral.com)
  • The profound alterations of the transcriptome and proteome introduced by RNA editing may thus help to solve a long lasting biological paradigm, namely, how biological complexity can be achieved with an almost constant number of genes: editing-induced alterations of splice patterns and coding potential of mRNAs may, together with alternative splicing, contribute to the formation of a complex proteome from a limited number of genes. (frontiersin.org)
  • The biological significance of RNA editing in pharmacokinetics/pharmacodynamics (PK/PD)-related genes is starting to be demonstrated. (ovid.com)
  • This review summarizes the current knowledge on the RNA editing that affects the expression and function of drug response-related genes. (ovid.com)
  • Targeted mutagenesis, editing of endogenous maize ( Zea mays ) genes, and site-specific insertion of a trait gene using clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas)-guide RNA technology are reported in maize. (plantphysiol.org)
  • Proviral effects are due in part to editing of viral RNAs ( Wong and Lazinski, 2002 ) and/or to destabilizing dsRNA resulting in suppression of dsRNA-signaling through MDA5 and MAVS to type I IFN genes ( Figure 1 ). (elifesciences.org)
  • Transcripts from more than 20 genes were edited in the chloroplast of Anthoceros formosae. (nii.ac.jp)
  • About 90 sites of RNA editing were found in the transcripts of 14 genes in the chloroplasts from Pteridium. (nii.ac.jp)
  • Publications] M.Kapoor: 'Organization of chloroplast ribosomal RNA genes and in vitro self-splicing activity of the large subunit rRNA intron from the green alga Chlorella'Curr. (nii.ac.jp)
  • Our study of RNA editing in four selected mitochondrial genes show a wide spectrum of divergent RNA editing frequencies including a dominance of U-to-C over the canonical C-to-U editing in some taxa like the order Schizaeales. (biomedcentral.com)
  • Similar purifying selections constitute the dominant evolutionary force at the editing sites of essential genes, such as the psa, some psb and pet groups, and a positive selection occurred in the editing sites of nonessential genes, such as most ndh and a few psb genes. (biomedcentral.com)
  • Comparative sequence analysis of genomic and complementary DNA clones from several mitochondrial genes in the higher plant Oenothera revealed nucleotide sequence divergences between the genomic and the messenger RNA-derived sequences. (harvard.edu)
  • Most mitochondrial mRNAs in kinetoplastids require editing, that is, the posttranscriptional insertion and deletion of uridine nucleotides that are specified by guide RNAs and catalyzed by multiprotein complexes. (nih.gov)
  • RNA editing refers to processes that change the identities of nucleotides and processes that add or delete nucleotides from RNAs. (pnas.org)
  • RNA editing may include the insertion, deletion, and base substitution of nucleotides within the RNA molecule. (wikipedia.org)
  • Besides the different families of sncRNAs, a large proportion of the mammalian transcriptome includes RNA transcripts not coding for proteins, longer than 200 nucleotides, and defined as long non-coding RNAs (lncRNAs) ( Fatica and Bozzoni, 2014 ). (frontiersin.org)
  • Deletion analysis determined that editing requires 5' portion of intron B. The predicted minimum fragment required for editing to occur contains inverted repeat structure separated by 120 nucleotides. (wikipedia.org)
  • Typically, a single RNA splicing reaction removes a large block of contiguous sequence, whereas each RNA editing reaction changes only one or two nucleotides. (pubmedcentralcanada.ca)
  • Here, we perform a comparative editome study in human and rhesus macaque and uncover a substantial proportion of macaque A-to-I editing sites that are genomically polymorphic in some animals or encoded as non-editable nucleotides in human. (springer.com)
  • MicroRNAs (miRNAs) are short RNAs of around 22 nucleotides that regulate gene expression. (biomedcentral.com)
  • In the mitochondria from Lycopodium, 5 sites of RNA editing were found in the region of 420 nucleotides of cox1 transcript. (nii.ac.jp)
  • Taken together, the data show that our GE system represents a safe and promising technology for editing specific nucleotides, correcting genetic mutations or other clinically relevant applications, independent of DSB and HDR, with potential therapeutic value in non-dividing cells. (rutgers.edu)
  • In a 2013 Nature Biotechnology paper , Joung and his colleagues reported finding that CRISPR-Cas RNA-guided nucleases could also induce double-strand breaks at sites with significant differences from the target site, including mismatches of as many as five nucleotides. (rna-seqblog.com)
  • These results have implications for the use of base editors in both research and clinical settings, illustrate the feasibility of engineering improved variants with reduced RNA editing activities, and suggest the need to more fully define and characterize the RNA off-target effects of deaminase enzymes in base editor platforms. (massgeneral.org)
  • Furthermore, the association of ADAR1p110 with RNase H2 suggests that the enzymes collaborate to resolve telomeric RNA-DNA hybrids. (scienceboard.net)
  • Adenosine deaminases acting on RNA (ADARs) are the RNA editing enzymes responsible for A-to-I editing. (wikipedia.org)
  • ADARs are RNA editing enzymes that target double-stranded regions of nuclear-encoded RNA and viral RNA. (pubmedcentralcanada.ca)
  • To investigate the possibility of reducing or eliminating unwanted RNA edits, the MGH team screened 16 editors with engineered versions of the deaminase enzymes, identifying two that were as efficient as the original version in inducing on-target DNA effects while inducing markedly fewer RNA edits. (massgeneral.org)
  • Expression levels of editing enzymes and their isoforms can explain some, but not all of this variation. (biomedcentral.com)
  • The Salk team decided to search bacterial genomes for new CRISPR enzymes that could target RNA, which could then be engineered to address problems with RNA and resulting proteins. (salk.edu)
  • In doing so, they discovered a family of CRISPR enzymes that targets RNA, and called it Cas13d. (salk.edu)
  • RNA molecules form the bridge between the stable genetic information contained within DNA and enzymes and proteins that carry out much of the metabolism within the cell. (abebooks.com)
  • Of all the RNA species, the nucleic acid intermediate, messenger RNA, is a desirable source of material to biologists, since this reflects much of, what ultimately, is translated into enzymes and proteins. (abebooks.com)
  • Compositions and methods for expanding CD34+ cells, performing research related to cancer stem cells, RNA-editing enzymes and for monitoring, diagnosing and treating, ameliorating and preventing diseases such as cancers or inflammatory diseases. (patents.com)
  • OAS isoforms (OAS1, OAS2, OAS3) are IFN inducible enzymes that sense dsRNA and produce 2',5'-oligoadenylates (2-5A) which activate RNase L to degrade viral and host single-stranded RNAs leading to apoptosis and inhibition of virus growth ( Silverman and Weiss, 2014 ). (elifesciences.org)
  • 2003) Dynamic association of RNA-editing enzymes with the nucleolus. (oalib.com)
  • RNA editing by base deamination: more enzymes, more targets, new mysteries. (surrey.ac.uk)
  • The recent identification of tRNA-specific adenosine deaminases (ADATs) has led to the suggestion that these enzymes, as well as the cytidine and adenosine deaminases acting on pre-mRNAs (CDARs and ADARs), belong to a superfamily of RNA-dependent deaminases. (surrey.ac.uk)
  • Virtually all editing activity is located in non-coding repetitive elements, which readily pair with inverted copies of the same repeat to form double-stranded RNA (dsRNA) substrates that are the preferred targets of the editing enzymes [ 28 ]. (biomedcentral.com)
  • By comparing DNA and RNA sequences from the squid brain, the team found that 60 percent of the RNA transcripts had been edited. (mbl.edu)
  • Editing of these non-coding sites is thought to have a critical role in protecting against activation of innate immunity by self-transcripts. (nature.com)
  • Typical PPR proteins are targeted to chloroplasts or mitochondria, bind organellar transcripts, and influence their expression by altering RNA sequence, turnover, processing, or translation ( 10 ). (pnas.org)
  • Virtually the entire collection of primary RNA transcripts, including the ncRNA fraction, can undergo post-transcriptional modifications as alternative splicing or RNA editing. (frontiersin.org)
  • Editing occurs in 100% of transcripts in human brain. (wikipedia.org)
  • Cancer cells create tumor-specific transcripts through dysregulation of posttranscriptional processes such as alternative splicing, 3′ processing, and RNA editing ( 3 ). (sciencemag.org)
  • In higher plants, RNA editing is a C-to-U conversion that corrects chloroplast and mitochondrial transcripts that are otherwise defective. (cornell.edu)
  • Here, a transcriptome-wide search for editing sites in nuclear transcripts of Arabidopsis ( Arabidopsis thaliana ) was performed. (biomedcentral.com)
  • Besides cytidine (C)-to-uridine (U) editing in mitochondrial transcripts, many nuclear transcripts were found to be diversely edited. (biomedcentral.com)
  • The editing events of some nuclear transcripts are highly enriched surrounding the borders between coding sequences (CDSs) and 3′ untranslated regions (UTRs), suggesting site-specific editing. (biomedcentral.com)
  • To our knowledge, the results provide the first global view of RNA editing in plant nuclear transcripts. (biomedcentral.com)
  • The data presented could serve as a repository for further analyses, and it will lead to a shift of RNA editing research from well-characterized mitochondrial and plastid transcripts to nuclear transcripts in plants. (biomedcentral.com)
  • We find that tissue specificity of editing largely reflects differential expression of substrate transcripts across tissues. (biomedcentral.com)
  • We identified a surprising enrichment of editing in intronic regions of brain transcripts, that could account for previously reported higher levels of editing in brain. (biomedcentral.com)
  • In contrast to the hyper-editing of many adenosine residues in close proximity, site-selective editing tends to occur consistently at specific residues, and even within the coding sequence of transcripts. (biomedcentral.com)
  • In their work, the researchers analyzed the newest version ABE called ABEmax in a way that included all cellular RNA transcripts in a human cell line-and they did it with more sensitive tools than others had used. (phys.org)
  • The fluorescent PPE products of edited and unedited transcripts were separated on denaturing gels (12% polyacrylamide and 7 m urea) and imaged with a fluorescence imager. (plantphysiol.org)
  • RNA editing is a post-transcriptional process that alters the nucleotide sequence of RNA transcripts to generate transcriptome diversity. (ovid.com)
  • Six out of 99 (6%) miRNA transcripts from which data were obtained were subject to A-to-I editing in at least one tissue. (biomedcentral.com)
  • Extensive RNA editing was found in atpB transcripts in the chloroplasts from 4 kinds of lycopsids, which included U to C conversion. (nii.ac.jp)
  • Publications] K.Yoshinaga: 'Extensive RNA editing and possible double-stranded structures dtermining editing sites in the atpB transcripts of hornwort chloroplasts'Nucleic Acids Res. (nii.ac.jp)
  • A rapid new assay to detect RNA editing reveals antipsychotic-induced changes in serotonin-2C transcripts. (ox.ac.uk)
  • A functionally critical position (Q/R site) of the AMPA receptor subunit GluR-B is controlled by RNA editing that operates in the nucleus, since in brain and clonal cell lines of neural origin, unspliced GluR-B transcripts occur edited in the Q/R site CAG codon and, additionally, in intronic adenosines. (semanticscholar.org)
  • Moreover, A-to-I editing of both the MDM2 regulatory microRNA and its binding site within the 3' UTR region stabilizes MDM2 transcripts, thereby enhancing blast crisis progenitor propagation. (diagenode.com)
  • Here, we applied in situ sequencing to distinguish between edited and unedited transcripts in distinct regions of the mouse brain at four developmental stages, and investigate the diversity of the RNA landscape. (biomedcentral.com)
  • This approach revealed cell-type-specific regulation of RNA editing of a set of transcripts, and developmental and regional variation in editing levels for many of the targeted sites. (biomedcentral.com)
  • Interestingly, many codon-altering RNA editing sites, recoding editing, are found in transcripts crucial for functional neurotransmission and brain function [ 6 ]. (biomedcentral.com)
  • The level of recoding editing at a site within a transcript is generally not 100%, so therefore unedited and edited transcripts are present in the same tissue, increasing the proteome diversity which is likely to contribute to the functional complexity of neural cells. (biomedcentral.com)
  • RNA editing in plant mitochondria -connecting RNA target sequences and acting proteins. (nature.com)
  • Re-infection triggers the complementary mature CRISPR RNA (crRNA) to find a matching sequence - which provides the CRISPR-associated (Cas) nuclease the specificity to form a double-strand break at specific "foreign" DNA sequences. (sigmaaldrich.com)
  • A team from UC San Diego is also working to correct mistakes in RNA to treat a group of diseases that are caused by too many repeats in RNA sequences, causing the RNA to clump together in cells. (fiercebiotech.com)
  • The RNA-targeted CRISPR managed to clear the majority of clumps and errant RNA sequences in models of Huntington's and a type of ALS. (fiercebiotech.com)
  • therefore, current methods to detect A-to-I editing sites align RNA sequences to their corresponding DNA regions and identify A-to-G mismatches. (nih.gov)
  • RNA editing (also RNA modification) is a molecular process through which some cells can make discrete changes to specific nucleotide sequences within an RNA molecule after it has been generated by RNA polymerase. (wikipedia.org)
  • Although A-to-I editing can occur in both coding and non-coding RNAs, recent findings, based on RNA-seq experiments, have clearly demonstrated that a large fraction of RNA editing events alter non-coding RNAs sequences including untranslated regions of mRNAs, introns, long non-coding RNAs (lncRNAs), and low molecular weight RNAs (tRNA, miRNAs, and others). (frontiersin.org)
  • During the editing process, adenosines that reside in the coding sequence (e.g. 5-HT2c receptor, glutamate receptor) or in non-repetitive intronic sequences (e.g. phosphodiesterase subtype 8A/PDE8A) are deaminated. (springer.com)
  • 1997 ), the editing process of the intronic sequences has been proposed to influence both RNA splicing pattern and formation of different isoforms of microRNAs, known to actively modulate gene expression (Kawahara et al. (springer.com)
  • Editing in both coding and noncoding sequences results in diseases ranging from cancers to neurological abnormalities. (mdpi.com)
  • Cellular editing of RNA can lead to the recoding of expressed sequences before they mature to their functional gene products, such as proteins or regulatory RNAs, and represents a hidden layer of genetic information and regulation. (caister.com)
  • Sequences corresponding to gRNA were also found in the same RNA. (nii.ac.jp)
  • 2010) Alu sequences in undifferentiated human embryonic stem cells display high levels of A-to-I RNA editing. (oalib.com)
  • For example, only a few thousand sites in human coding sequences were found so far, most of them weakly edited, and only a few dozen sites are conserved across mammals [ 27 ]. (biomedcentral.com)
  • Bass, B. L. RNA editing by adenosine deaminases that act on RNA. (nature.com)
  • Deaminases can also alter RNA , the group reports today in Nature . (sott.net)
  • And they've already engineered deaminases that substantially reduce the number of inadvertent RNA edits. (sott.net)
  • David Liu, a Harvard University chemist who created the first base editor and co-founded two companies based on the technology with Joung, notes that deaminases naturally edit cellular RNA, stressing that the biological consequences of such editing are unclear . (sott.net)
  • Both Liu and Joung stress that their labs have found deaminases that work only on either DNA or RNA, which makes them confident that they can decouple the off-target effects seen with the current base editors. (sott.net)
  • RNA editing by adenosine deaminases that act on RNA converts adenosines to inosines in coding and non-coding regions of mRNAs. (frontiersin.org)
  • Collectively, our data show for the first time that RNA-guided cytidine deaminases are capable of programmable single and multiplex base editing in an invertebrate model. (g3journal.org)
  • In this review we describe the mechanisms of RNA editing and focus on target mRNAs of editing that are functionally relevant to normal and aberrant CNS activity. (frontiersin.org)
  • Besides mRNAs, also primary and precursor miRNAs can be targets for RNA editing by ADARs. (frontiersin.org)
  • Editing of pri- and pre-miRNAs can alter their processing but also their base-pairing potential with target mRNAs. (frontiersin.org)
  • Therefore, editing of miRNAs can indirectly change the abundance and translatability of their target mRNAs. (frontiersin.org)
  • Editing of mRNAs was originally believed to be a rare event. (frontiersin.org)
  • In plant organelles, specific messenger RNAs (mRNAs) are subjected to conversion editing, a process that often converts the first or second nucleotide of a codon and hence of the encoded amino acid. (cam.ac.uk)
  • RNA editing produces mature mRNAs in the mitochondria of trypanosomatids by guide RNA (gRNA)-directed posttranscriptional insertion and deletion of uridylates (U's) ( 2 ). (asm.org)
  • The mRNAs for components of respiratory complex I are preferentially edited in the mammalian stage of the life cycle, where the trypanosomes lack cytochromes, rely on glycolysis for energy production, and utilize complex I and alternate oxidase for terminal respiration. (asm.org)
  • In contrast, the invertebrate stage predominantly utilizes cytochrome-mediated oxidative phosphorylation for energy generation while editing cytochrome mRNAs only in this stage. (asm.org)
  • A large proportion of the recoding events mediated by RNA editing are in mRNAs that encode ion channels and transporters. (caister.com)
  • A-to-I editing have the potential to diversify the code of mRNAs since I is read as guanosine during translation. (neurodegenerationresearch.eu)
  • In addition we show that hyper-edited mature mRNAs are retained in the nucleus and are associated with p54nrb. (oalib.com)
  • Athanasiadis A, Rich A, Maas S (2004) Widespread A-to-I RNA editing of Alu-containing mRNAs in the human transcriptome. (oalib.com)
  • The posttranscriptional modification of messenger RNA precursors (pre-mRNAs) by base deamination can profoundly alter the physiological function of the encoded proteins. (surrey.ac.uk)
  • RNA editing by C-to-U conversions is nearly omnipresent in land plant chloroplasts and mitochondria, where it mainly serves to reconstitute conserved codon identities in the organelle mRNAs. (biomedcentral.com)
  • In most cases, RNA editing affects organelle mRNAs, where evolutionarily conserved codons are restored. (biomedcentral.com)
  • Leveraging Isis' expertise in developing RNA-targeted compounds, together the team has demonstrated that we can develop molecules that enhance the effectiveness of the CRISPR mechanism. (innovations-report.com)
  • In vertebrates, editing is rare and usually consists of a small number of changes to the sequence of the affected molecules. (wikipedia.org)
  • To identify diverse post-transcriptional modifications of RNA molecules and determine the transcriptome-wide landscape of RNA modifications by means of next generation RNA sequencing, recently many studies have developed conventional or specialised sequencing methods. (wikipedia.org)
  • Moreover, mass spectrometry allows the investigation of modification dynamics by labeling RNA molecules with stable (non-radioactive) heavy isotopes in vivo. (wikipedia.org)
  • The study revealed that a lack of RNA editing, a process by which information inside RNA molecules is transformed, leads to tumor growth and progression through manipulation of proteins. (healthcanal.com)
  • Key molecular methods that provide the means to initially isolate and analyze RNA molecules are the focus of this volume. (abebooks.com)
  • Transfer RNAs (tRNAs) are critical players in gene expression due to their essential function as adaptor molecules. (caister.com)
  • Besides the common right-handed B- or A- structures, the alternate Z-conformation, which is left-handed, can be formed in both DNA and RNA molecules. (ntu.edu.sg)
  • Target base editing (red arrows), target sequence (black), PAM region (green), target sites (red), mutant amino acid (underlined) and amino acid mutation type are indicated. (nature.com)
  • Kleinberger, Y. & Eisenberg, E. Large-scale analysis of structural, sequence and thermodynamic characteristics of A-to-I RNA editing sites in human Alu repeats. (nature.com)
  • Unlike alternative splicing which shuffles large chunks of sequence around, RNA editing targets single bases. (icr.org)
  • Ultra-edited RNAs exhibit the known sequence motif of ADARs and tend to localize in sense strand Alu elements. (nih.gov)
  • Zhang and colleagues introduced the risk-associated APOE4 RNA into cells and showed that RESCUE can convert its signature Cs to an APOE2 sequence, essentially converting a risk to a non-risk variant. (sciencecodex.com)
  • Even with recent developments in massively parallel DNA sequencing technologies ( 9 ), it still remains expensive to sequence whole genomes and transcriptomes, both of which are required to identify RNA editing targets. (sciencemag.org)
  • The solution structure of the ADAR2 dsRBM-RNA complex reveals a sequence specific readout of the minor groove. (wikipedia.org)
  • Like RNA splicing, RNA editing alters the sequence of an RNA from that encoded in the DNA. (pubmedcentralcanada.ca)
  • Thus, ADARs change the primary sequence information in an RNA. (pubmedcentralcanada.ca)
  • Conceivably, ADARs could affect any biological process that involves sequence- or structure-specific interactions with RNA, and ultimately, numerous roles of ADARs may be discovered. (pubmedcentralcanada.ca)
  • RNAs are cleaved, ligated, and deaminated on their way to maturation, and in some cases, their sequence is even altered in the brief moment when RNA polymerase stalls. (oup.com)
  • In addition to its functional role, AZIN1 editing levels may be one of the important facilitators of adenoma-carcinoma sequence in CRC and serve as an important clinical biomarker in this disease. (aacrjournals.org)
  • Nucleotide sequence modification through single base editing in animals is emerging as an important player in tumorigenesis. (garvan.org.au)
  • Sequence editing impacts development, including pluripotency and hematopoiesis, and multiple recent studies have shown that dysregulation of editing is associated with tumor biology. (garvan.org.au)
  • Much is yet to be learned about the role of sequence editing in human biology but this process is a critical modulator of cell regulation and may present an attractive option for therapeutic intervention in cancer in the future. (garvan.org.au)
  • SIGNIFICANCE: Sequence editing provides an additional regulatory layer of cancer initiation and progression that may be amenable to therapeutic design. (garvan.org.au)
  • This review highlights the cellular processes controlled by sequence editing, their implications in normal and cancerous states and considers potential targeted therapeutic strategies. (garvan.org.au)
  • By using repair DNA templates that contain sequence variation or promote the insertion of expression cassettes, gene editing, and site-specific gene integration can be achieved. (plantphysiol.org)
  • This process can be so extensive that most of the coding sequence, as well as the initiation and termination codons, results from RNA editing ( 1 , 11 , 27 , 28 , 30 ). (asm.org)
  • They are characterised by tandem 30-40 amino acid motifs that form an extended binding surface capable of sequence-specific recognition of RNA strands. (ovid.com)
  • We have conducted a survey of RNA editing of miRNAs from ten human tissues by sequence comparison of PCR products derived from matched genomic DNA and total cDNA from the same individual. (biomedcentral.com)
  • Pri-miRNAs contain a short double-stranded RNA (dsRNA) stem-loop formed between the miRNA sequence and its adjacent complementary sequence. (biomedcentral.com)
  • RNA editing is the site-specific modification of an RNA sequence to yield a product differing from that encoded by the DNA template. (biomedcentral.com)
  • RNA editing is a posttranscriptional modification process that alters the RNA sequence so that it deviates from the genomic DNA sequence. (biomedcentral.com)
  • In 1994, Davidson's team showed that one mechanism of RNA editing is the deamination of cytosine to uracil, which is catalyzed by the Apobec family, including Apobec-1. (asbmb.org)
  • Deamination type editing has been found in all kingdoms of life. (frontiersin.org)
  • Finally, ADARs are now being adapted for RNA engineering purposes. (nature.com)
  • Fig. 7: Utilizing ADARs for RNA probing and engineering. (nature.com)
  • Thomas, J. M. & Beal, P. A. How do ADARs bind RNA? (nature.com)
  • ADARs contain multiple double-stranded RNA (dsRNA)-binding domains and a separate catalytic domain. (scienceboard.net)
  • All ADARs share common modular organisation of domain structures that comprise a double-stranded RNA-binding domain (dsRBD) necessary for target binding and a catalytic domain conveying deaminase activity (Gallo et al. (springer.com)
  • So far, ADARs have been definitively shown to alter the meaning of codons, create splice sites, and sequester an RNA to the nucleus. (pubmedcentralcanada.ca)
  • In all organisms editing by ADARs is most abundant in the nervous system. (frontiersin.org)
  • Conclusions These findings highlight the fact that the differentially expressed ADARs in tumours, which are responsible for an A to I editing imbalance, has great prognostic value and diagnostic potential for HCC. (bmj.com)
  • One type of RNA editing events, the A-to-I editing, is catalyzed by adenosine deaminase acting on RNA (ADARs) acting on dsRNAs. (springer.com)
  • Editing by ADARs is highly prevalent across the Metazoa, mostly targeting dsRNA structures formed by genomic repeats. (biomedcentral.com)
  • When transcribed, interaction between two Alus that are in opposite orientation gives rise to double-stranded RNA (dsRNA). (iu.edu)
  • Although the presence of dsRNA in the cell was previously thought to only occur during viral infection, it is now known that cells express many endogenous small dsRNAs, such as short interfering RNA (siRNAs) and microRNA (miRNAs), which regulate gene expression. (iu.edu)
  • While several recent studies have suggested the potential crosstalk between RNA editing and other regulatory processes, such as alternative splicing, piRNA biogenesis and cytosolic dsRNA response [ 10 , 11 , 13 , 14 ], an in-depth functional perspective of the widespread A-to-I editing sites in primate evolution remain to be addressed. (springer.com)
  • Zhang Z, Carmichael GG (2001) The fate of dsRNA in the nucleus: a p54(nrb)-containing complex mediates the nuclear retention of promiscuously A-to-I edited RNAs. (oalib.com)
  • Clusters of editing sites are abundant in repetitive genomic regions that putatively form double-stranded RNA (dsRNA) structures and are rarely seen in coding regions. (biomedcentral.com)
  • The strong association of RNA editing with the long dsRNA regions originating from non-coding repetitive elements is contrasted by the almost non-existing signal seen in coding regions. (biomedcentral.com)
  • b - e Representative sequencing chromatograms at the Mstn , Dmd , Tia1-1 , and Tia1-2 targets of WT and edited rabbit blastocysts. (nature.com)
  • A team from the Broad Institute has devised a CRISPR-based system that targets RNA in a way that makes reversible changes to DNA possible. (fiercebiotech.com)
  • RESCUE targets one of the four main "bases" of RNA, cytosine. (fiercebiotech.com)
  • This efficient approach greatly expands the repertoire of RNA editing targets and can be applied to studies involving RNA editing-related human diseases. (sciencemag.org)
  • The limiting factor in the identification of RNA editing targets has been the number of locations that could be profiled by the sequencing of DNA and RNA samples. (sciencemag.org)
  • To reduce biases in detection, the key criteria for previous predictions of editing targets-conservation, coding potential, and RNA secondary structure( 11 - 15 )-were not taken into account. (sciencemag.org)
  • Over 90% of the previously identified editing targets are present in this data set (table S1). (sciencemag.org)
  • We discovered that in the nucleus, ADAR1p110 oversees a similar mechanism to ADAR1p150, the better-known cytoplasmic variant, but the editing process in this case targets particular nucleic acid structures called R-loops when formed at the chromosome ends," said Kazuko Nishikura, PhD, professor in the Gene Expression & Regulation Program of the Wistar Institute Cancer Center, in a statement. (scienceboard.net)
  • Novel identifications of long noncoding RNA and retrotransposons as editing targets further expand the effects of A-to-I editing. (mdpi.com)
  • One of the most important RNA editing gene targets is the antizyme inhibitor 1 (AZIN1), and edited AZIN1 promotes accumulation of ornithine decarboxylase and polyamines, leading to promotion and development of carcinogenesis. (aacrjournals.org)
  • So a drug that targets toxic RNAs or RNAs resulting from improper splicing could have a life-changing impact for people with these types of devastating diseases. (salk.edu)
  • Finally, we discuss some of the emerging targets for editing and how this process may be used to regulate nervous function in response to a variable environment. (caister.com)
  • Accurate prediction of the RNA targets of pentatricopeptide repeat (PPR) proteins requires accurate annotation of their RNA-binding motifs. (ovid.com)
  • Our results indicate that RNA editing increases the diversity of miRNAs and their targets, and hence may modulate miRNA function. (biomedcentral.com)
  • Contrary to the classical "central dogma" of molecular biology, genetic information does not always pass faithfully from genomic DNA to messenger RNA to the synthesis of proteins. (mbl.edu)
  • However, such methods perform poorly on RNAs that underwent extensive editing ("ultra"-editing), as the large number of mismatches obscures the genomic origin of these RNAs. (nih.gov)
  • The authors also did not observe any A to non-G editing above that of untreated cells among the 17 genomic sites tested. (genomeweb.com)
  • A comprehensive set of several hundred human RNA editing sites was detected by comparing genomic DNA with RNAs from seven tissues of a single individual. (sciencemag.org)
  • We first compiled a set of 59,437 genomic locations enriched with RNA editing sites, excluding repetitive regions such as Alu (fig. S1) ( 10 ). (sciencemag.org)
  • Amplified RNA (double-stranded cDNA) was labeled with cy3 or cy5 following the Agilent Genomic DNA Labeling Kit Plus procedure (Product No. 5188-5309). (sigmaaldrich.com)
  • A single genomic copy of the editase allows efficient editing with sufficient specificity. (europa.eu)
  • To search for RNA-editing sites in human miRNAs, PCR product sequencing was performed from matched total cDNA and genomic DNA isolated from adult human brain, heart, liver, lung, ovary, placenta, skeletal muscle, small intestine, spleen and testis. (biomedcentral.com)
  • A genomic error that causes Rett Syndrome, a serious lifelong neurological disorder, can be corrected in the brains of mice by rewriting the genetic instructions carried by the RNA. (technologynetworks.com)
  • Therefore, the double-stranded precursors of miRNAs may be substrates for A-to-I editing. (biomedcentral.com)
  • Given these many mechanisms for regulating editing levels, generally or for specific substrates, there are many ways to generate a diverse editing landscape. (biomedcentral.com)
  • First, the gRNA requires 17-21 bases of RNA-to-DNA homology, which is called the protospacer. (sigmaaldrich.com)
  • The antibodies cause a supershift of previously identified gRNA-specific ribonucleoprotein complexes and immunoprecipitate in vitro RNA editing activities that insert and delete uridylates. (asm.org)
  • The editing window of BE3 reached up to 13 bases (from C1 to C13 in the range of gRNA) in B. mori . (g3journal.org)
  • The gRNA can be generated in various forms using different methods: gRNA can be expressed from a plasmid as a single guide RNA (sgRNA), transcribed in vitro as an sgRNA (IVT sgRNAs), or chemically synthesized as an sgRNA or two-part complex (crRNA duplexed with tracrRNA). (idtdna.com)
  • Chemically synthesized gRNAs can be modified to enhance editing efficiency by stabilizing the gRNA against nuclease degradation, and also by reducing the risk of an innate immune response often seen with IVT sgRNAs. (idtdna.com)
  • In this webinar, Ashley Jacobi compares the on-target and off-target editing events observed with different gRNA formats in transformed and primary cell lines. (idtdna.com)
  • Every editing site was determined by guide RNA (gRNA) which located in the same RNA. (nii.ac.jp)
  • RNA editing occurs in the cell nucleus and cytosol, as well as within mitochondria and plastids. (wikipedia.org)
  • RNA editing occurs in the cell nucleus, cytosol, as well as in mitochondria and plastids, which are thought to have evolved from prokaryotic-like endosymbionts. (morebooks.de)
  • Almost all of them are post-translationally targeted to plastids and mitochondria, where they play important roles in post-transcriptional processes including splicing, RNA editing and the initiation of translation. (ovid.com)
  • In the mitochondria of A. formosae, 30 editing sites were observed in 420 bases region of cox1 transcript. (nii.ac.jp)
  • Moreover, while editing rates in the two organelles are usually correlated, we observe uncoupled evolution of editing frequencies in fern mitochondria and chloroplasts. (biomedcentral.com)
  • C-to-U and U-to-C RNA editing in fern chloroplasts and mitochondria follow disinct evolutionary pathways that are surprisingly different from what has previously been found in flowering plants. (biomedcentral.com)
  • This editing suggests that the standard genetic code is used in plant mitochondria and resolves the frequent coincidence of CGG codons and tryptophan in different plant species. (harvard.edu)
  • The apparently frequent and non-species-specific equivalency of CGG and TGG codons in particular suggests that RNA editing is a common feature of all higher plant mitochondria. (harvard.edu)
  • A transcript is a stretch of DNA transcribed into an RNA molecule. (mbl.edu)
  • These studies have shown that RNA is not only an essential intermediate in the flux of genetic information from DNA to proteins, but rather is a molecule involved in a plethora of fundamental cellular processes. (frontiersin.org)
  • The term RNA editing describes those molecular processes in which the information content in an RNA molecule is altered through a chemical change in the base makeup. (morebooks.de)
  • In flowering plants, RNA editing converts cytidines to uridines in the RNAs transcribed from the chloroplast and mitochondrial genomes ( 3 ). (pnas.org)
  • Stage-specific RNA editing appears to regulate mitochondrial respiration in the different life stages of African trypanosomes ( 9 , 29 ). (asm.org)
  • Mitochondrial RNAs in the acellular slime mold Physarum polycephalum are subject to the widest range of editing events observed thus far. (caister.com)
  • At least three distinct editing mechanisms are needed to account for the different forms of editing observed in the mitochondrial transcriptome: nucleotide insertions and deletions, C to U changes, and specific alterations at the 5' end of tRNAs. (caister.com)
  • The rare instances of base changes and replacement of the first nucleotide of mitochondrial tRNAs are not directly linked to transcription and are likely to occur via processes related to those previously described in other mitochondrial editing systems. (caister.com)
  • No RNA editing was found in the mitochondrial cox1 transcript from 4 kinds of liverworts. (nii.ac.jp)
  • Most mitochondrial RNA editing sites are shared between the recently emerging fern orders whereas chloroplast editing sites are mostly clade-specific. (biomedcentral.com)
  • RNA editing mainly occurs in chloroplasts and mitochondrial genomes, and the number of editing sites varies in terrestrial plants. (biomedcentral.com)
  • Recently, the multiprotein mitochondrial RNA binding complex 1 (MRB1) has emerged as a key player in this process. (escholarship.org)
  • Manipulation of the miRNAs by silencing the naturally occurring or wild-type version of a miRNA and overexpressing an "edited" miRNA confirmed the significance of RNA editing in tumor growth and metastasis. (healthcanal.com)
  • RNA editing in the precursor microRNAs (pre-miRNAs) of ath-miR854 family, resulting in secondary structure transformation, implies its potential role in microRNA (miRNA) maturation. (biomedcentral.com)
  • In this study we have systematically investigated the presence of RNA editing in miRNAs. (biomedcentral.com)
  • These data reveal a dual mechanism governing malignant transformation of progenitors that is predicated on hyper-editing of cell-cycle-regulatory miRNAs and the 3' UTR binding site of tumor suppressor miRNAs. (diagenode.com)
  • Transfer RNAs (tRNAs) and ribosomal RNAs (rRNA), for instance, are essential components of translational machinery and highly abundant in all living cells. (frontiersin.org)
  • MODOMICS: a database of RNA modification pathways. (nature.com)
  • Courtesy of Nick Davidson RNA editing can create heterogeneity in genetically identical cells by mediating amino acid substitutions, alternative isoform creation and modification of stop codons. (asbmb.org)
  • Many of these methods are based on specific capture of the RNA species containing the specific modification, for example through antibody binding coupled with sequencing of the captured reads. (wikipedia.org)
  • This method, called NAIL-MS (nucleic acid isotope labeling coupled mass spectrometry), enables a variety of approaches to investigate RNA modification dynamics. (wikipedia.org)
  • Pseudouridylation of nonsense codons suppresses translation termination both in vitro and in vivo, suggesting that RNA modification may provide a new way to expand the genetic code. (wikipedia.org)
  • These results demonstrate a causal relationship between RNA editing and the development of cardiovascular disease indicating that a single epitranscriptomic RNA modification can maintain cardiovascular health. (medworm.com)
  • RNA editing is a site specific, post transcriptional modification of RNA. (frontiersin.org)
  • This editing is a widespread post-transcriptional modification event in animals. (paper.edu.cn)
  • One of the key steps in any gene modification experiment, such as gene silencing or gene editing, is the introduction of RNA into your cell line or in vivo system. (horizondiscovery.com)
  • One way to help identify causal variants is to study RNA editing, a post-transcriptional modification to an RNA nucleotide. (arvojournals.org)
  • Also included are studies employing bioinformatics to identify and predict RNA editing sites as well as the evolution of RNA modification. (caister.com)
  • An essential text for anyone interested in RNA editing and modification, RNA structure and function, post-transcriptional regulation, and the regulation of gene expression and a recommended purchase for molecular biology libraries. (caister.com)
  • an essential book for anyone interested in RNA editing and modification, RNA structure and function, post-transcriptional regulation, and the regulation of gene expression. (caister.com)
  • F11R is subjected to RNA editing, a post-transcriptional modification which affects RNA structure, stability, localization, translation and splicing. (oalib.com)
  • RESCUE can be guided to any RNA of choice, then perform a C-to-U edit through the evolved ADAR2 component of the platform. (eurekalert.org)
  • These findings provide a platform for multiple therapeutic applications, especially for nervous system diseases, using successive application of designer CRISPR RNA drugs," said senior author Don Cleveland, PhD, Distinguished Professor and Chair of the Department of Cellular and Molecular Medicine at UC San Diego School of Medicine and head of Ludwig Cancer Research's Laboratory for Cell Biology. (innovations-report.com)
  • Experiments with GUIDE-seq showed it was sensitive enough to detect off-target sites at which CRISPR RNA-guided nucleases induced unwanted mutations of a gene that occur with a frequency of as little as 0.1 percent in a population of cells. (rna-seqblog.com)
  • GUIDE-seq was also able to identify breakpoint hotspots in control cell lines that were not induced to express the CRISPR RNA-guided nucleases. (rna-seqblog.com)
  • This is especially true in light of all the other intricate cellular information systems that RNA-editing interfaces with. (icr.org)
  • But the weaknesses of base editors have become increasingly apparent, and a new study shows they can also accidentally mutate the strands of RNA that help build proteins or perform other key cellular tasks. (sott.net)
  • RNA-editing is a tightly regulated, and essential cellular process for a properly functioning brain. (biomedcentral.com)
  • A team of researchers with the Broad Institute of Harvard and MIT has found evidence showing that using base editors can lead to unexpected RNA cellular edits. (phys.org)
  • Analysis and minimization of cellular RNA editing by DNA adenine base editors, Science Advances (2019). (phys.org)
  • RNA editing especially has increased greatly during mammalian evolution and modulates diverse cellular functions presumably in a context-dependent manner. (garvan.org.au)
  • RNA editing is a widespread post-transcriptional process contributing to greater cellular transcriptome diversity in eukaryotes. (bmj.com)
  • Additionally, editing in the non-coding region of a transcript can affect splicing, microRNA targeting, RNA degradation, translation, and other important cellular processes [ 2 ]. (biomedcentral.com)
  • Meanwhile, this strategy can be used to precisely mimic human pathologies by efficiently inducing nonsense or missense mutations as well as RNA mis-splicing in rabbit. (nature.com)
  • The team took the new platform into human cells, showing that they could target natural RNAs in the cell as well as 24 clinically relevant mutations in synthetic RNAs. (eurekalert.org)
  • As a strategy to restore the normal function of MECP2, the single-base RNA editing approach of swapping out A and G could address about 40% of all known mutations that cause Rett syndrome, Sinnamon said. (genengnews.com)
  • In this study, we have discovered an unexpected role for GUN1 in plastid RNA editing, as gun1 mutations affect RNA-editing efficiency at multiple sites in plastids during retrograde signaling. (pnas.org)
  • The team tested their tool against RNA mutations that cause Fanconi anemia and X-linked nephrogenic diabetes insipidus, finding that the system repaired the mutations. (fiercebiotech.com)
  • We engineered two CBE variants bearing mutations in rat APOBEC1 that substantially decreased the number of RNA edits (by more than 390-fold and more than 3,800-fold) in human cells. (massgeneral.org)
  • In a press conference call about the study, Liu said this kind of editing enables the efficient and permanent conversion of C-G base pairs to T-A base pairs, and addresses point mutations found in roughly 15 percent of genetic diseases. (genomeweb.com)
  • The researchers showed they could use RESCUE to target natural RNAs in cells, as well as "24 clinically relevant mutations in synthetic RNAs," they said in a statement . (fiercebiotech.com)
  • ABEs convert one DNA base pair into another, allowing for the repair of mutations in some cell types without generating undesired editing effects. (phys.org)
  • Progeny showed expected Mendelian segregation of mutations, edits, and targeted gene insertions. (plantphysiol.org)
  • Overall, we report a list of A-to-I editing events that recently originated through G-to-A mutations in primates, representing a valuable resource to investigate the features and evolutionary significance of A-to-I editing events at the population and species levels. (springer.com)
  • Recently, a group of A-to-I RNA editing sites has been reported in candidate gene studies to be genomically encoded as non-editable nucleotide in other closely related species [ 15 , 16 ], representing a recent birth or death process of RNA editing through DNA point mutations. (springer.com)
  • Because such off-target mutations could potentially lead to adverse effects, including cancer, the ability to identify and eventually minimize unwanted double-strand breaks would be essential to the safe clinical use of these RNA-guided nucleases, the authors noted. (rna-seqblog.com)
  • Understanding the range and number of off-target mutations in untransformed cells will give a better picture of how CRISPR-Cas RNA-guided nucleases and other tools would function in clinical applications. (rna-seqblog.com)
  • Compared to sites of mild editing, ultra-editing occurs primarily in Alu-rich regions, where potential base pairing with neighboring, inverted Alus creates particularly long double-stranded RNA structures. (nih.gov)
  • Aside from the propensity of RNA substrate to form hairpin structures, little is known about other mechanisms regulating this more selective form of editing. (biomedcentral.com)
  • RNA editing could change the secondary structures of 82 proteins, and create or eliminate a transmembrane region in five proteins as determined in silico . (biomedcentral.com)
  • Structures capturing distinct MRB1590 conformations reveal that the RNA binding pore adopts closed and open states, with the latter able to accommodate RNA. (escholarship.org)
  • This finding has the potential to transform the study of RNA function by paving the way for direct RNA transcript detection, analysis and manipulation. (eurekalert.org)
  • Our results reveal a fundamental connection between PAM binding and substrate selection by RCas9, and highlight the utility of RCas9 for programmable RNA transcript recognition without the need for genetically introduced tags. (eurekalert.org)
  • 2012. Transcript Diversification in the Nervous System: A to I RNA Editing in CNS Function and Disease Development . (icr.org)
  • RNA editing is a transcript-based layer of gene regulation. (biomedcentral.com)
  • Together, these data suggest a complex regulation of the RNA-editing process beyond transcript expression levels. (biomedcentral.com)
  • Indeed, it has recently been shown that the pri-miRNA transcript of human miRNA miR-22 is subject to A-to-I RNA editing in a number of human and mouse tissues [ 31 ]. (biomedcentral.com)
  • Finally, we show that an adenine base editor 7 can also induce transcriptome-wide RNA edits. (massgeneral.org)
  • NEW YORK (GenomeWeb) - A team of researchers from Massachusetts General Hospital led by Keith Joung has reported in a new study that CRISPR-Cas base editing technology can induce transcriptome-wide off-target RNA editing in human cells, along with off-target DNA edits. (genomeweb.com)
  • Recently, functional experiments have revealed many novel functional roles of RNA modifications. (wikipedia.org)
  • An accurate detection of A-to-I events occurring in non-coding RNAs is of utmost importance to clarify yet unknown functional roles of RNA editing in the context of gene expression regulation and maintenance of cell homeostasis. (frontiersin.org)
  • In addition, we performed a series of functional assays to elucidate the functional role of AZIN1 RNA editing in CRC pathogenesis. (aacrjournals.org)
  • Population genetics analyses of the focal editing sites further reveal that a portion of these young editing events are evolutionarily significant, indicating general functional relevance for at least a fraction of these sites. (springer.com)
  • Importantly, comprehensive characterization of this subset of RNA editome, if exists, could advance the evolutionary and functional interrogation of primate RNA editing regulation in the following regards. (springer.com)
  • Often, the recoding events are essential for the normal function of the gene product (for example creating an open reading frame), in other cases RNA editing creates additional variation and phenotypic diversity since both the edited and the non-edited versions of the product are functional and co-exist. (caister.com)
  • All the chapters here have been written by experts in the various research areas and describe key recent findings as well as exploring current frontiers in the mechanisms and functional roles of RNA editing. (caister.com)
  • However, the functional consequences of many of these RNA editing events are still unknown. (neurodegenerationresearch.eu)
  • For a long time, it was believed that the main functional impact of RNA editing is its recoding capacity, resulting in the introduction of novel proteins. (biomedcentral.com)
  • However, the transcribed messenger RNAs are extensively edited, creating functional diversity. (mysciencework.com)
  • Wedekind, J. E., Dance, G. S. C., Sowden, M. P. & Smith, H. C. Messenger RNA editing in mammals: new members of the APOBEC family seeking roles in the family business. (nature.com)
  • In 2017, Sinnamon and Mandel reported their first success with the RNA approach, efficiently repairing the Rett mouse mutant RNA in developing neurons in culture. (genengnews.com)
  • 2017. A-to-I RNA Editing in the Earliest-Diverging Eumetazoan Phyla . (icr.org)
  • RESCUE builds on another system developed at the Broad called RNA Editing for Programmable A to I Replacement (REPAIR), which Zhang's team reported in 2017. (fiercebiotech.com)
  • The presentation is part of session: Emerging Topics in RNA Biology on September 25, 2017 starting at 3:00pm CET. (pharmiweb.com)
  • Patterson JB, Thomis DC, Hans SL, Samuel CE (1995) Mechanism of interferon action: double-stranded RNA-specific adenosine deaminase from human cells is inducible by alpha and gamma interferons. (oalib.com)
  • Inosines are interpreted as guanosines and hence, this type of editing can change codons, alter splice patterns, or influence the fate of an RNA. (frontiersin.org)
  • Here we study the relationship between amino acid residues encoded by edited codons and the structural characteristics of these residues within proteins. (cam.ac.uk)
  • The findings of this paper were somewhat surprising, since A1cf was discovered as necessary for the deaminase Apobec-1 to act on RNA, and it was originally thought to be the Apobec-1 cofactor," Davidson said. (asbmb.org)
  • Although most researchers have focused on the DNA-editing activities of base editors, the deaminase in the most commonly used cytosine-to-thymine editor was originally identified for its ability to modify RNA. (massgeneral.org)
  • In fact, these SECURE (SElective Curbing of Unwanted RNA Editing) variants were even more precise than the unaltered deaminase in inducing the desired DNA edits. (massgeneral.org)
  • We have used a structural modelling approach to define 10 different variants of the PPR motif found in plant proteins, in addition to the putative deaminase motif that is found at the C-terminus of many RNA-editing factors. (ovid.com)
  • We need to know how much MECP2 RNA we need to repair in an individual cell and in how many cells in the nervous system," Mandel said. (genengnews.com)
  • But recently, MBL Whitman Investigator Joshua Rosenthal and colleagues discovered the most prolific usage yet of RNA editing in the common squid, Doryteuthis pealeii , a behaviorally sophisticated marine organism that has long been prized for studies of the nervous system. (mbl.edu)
  • 2,3 And as RNA editing is being studied more in humans, our knowledge of its importance in the nervous system is increasing. (icr.org)
  • 1 In fact, the researchers discovered that A-to-I RNA editing had a pervasive effect on most biochemical pathways in the squid, especially those related to the nervous system. (icr.org)
  • Other reports have demonstrated that RNA editing is crucial to the proper functioning of the nervous system in humans and other mammals. (icr.org)
  • Dysfunction of A-to-I RNA editing can have catastrophic effects, particularly in the central nervous system. (biomedcentral.com)
  • This pattern of evolutionary constraint suggests an important role of RNA-editing in the development and maintenance of the metazoan nervous system. (biomedcentral.com)
  • A to I editing is most abundant in the central nervous system (CNS). (frontiersin.org)
  • This type of editing has profound effects on gene expression and can lead to the creation of different forms of proteins or RNAs with different functions. (icr.org)
  • This type of editing in both coding and non-coding RNAs has been found to have profound effects on gene expression. (icr.org)
  • Researchers found that RNA editing events can have large downstream effects that influence gene expression and subsequent phenotypic manifestations of. (scienceboard.net)
  • By combining the data of A-I RNA editing and gene expression, we generated an algorithm that allowed discrimination between the group of patients who developed a treatment-emergent depression and those who did not. (springer.com)
  • 2005) Regulating gene expression through RNA nuclear retention. (oalib.com)
  • Sample RNA was eluted at a reduced volume of 40 µl with nuclease-free water, and subjected to a scaled-up (5X) RNase-free DNase digestion (Product No. AMPD1 ), for a final volume of 97 µl. (sigmaaldrich.com)
  • The ability to capture these RNA-guided nuclease-independent breaks suggests that GUIDE-seq could be a useful tool for studying and monitoring DNA repair in living cells. (rna-seqblog.com)
  • 4 ) make a strong case that RNA editing in chloroplasts contributes to a type of chloroplast-to-nucleus signaling defined by the genomes uncoupled ( gun ) mutants in Arabidopsis . (pnas.org)
  • Retrograde signaling and posttranscriptional RNA editing are important regulatory processes for chloroplast development and function in flowering plants. (pnas.org)
  • Finally, we observe that chloroplast RNA editing appears to be completely absent in horsetails (Equisetales), the sister clade of all other monilophytes. (biomedcentral.com)
  • Fig. 5: RNA editing generates transcriptomic diversity. (nature.com)
  • RNA-editing processes show great molecular diversity, and some appear to be evolutionarily recent acquisitions that arose independently. (wikipedia.org)
  • Numerous examples of RNAs known to be edited are provided throughout the volume, but most importantly, the book highlights the amazing mechanistic diversity found among the various types of RNA editing. (oup.com)
  • help to dispel any remaining ignorance for students and researchers who are interested in RNA processing and mechanisms for increasing genetic diversity alike. (oup.com)
  • In human cancers, aberrant post-transcriptional modifications, such as alternative splicing and RNA editing, may lead to tumour specific transcriptome diversity. (bmj.com)
  • Studies have shown that a large proportion of variants present in DNA are not present in the RNA and vice versa due to RNA-Editing - a process that displays great molecular diversity, and other unknown molecular processes. (labroots.com)
  • There is a need to discover new potential actionable genetic lesions, to which end, non-conventional cancer pathways, such as RNA editing, are worth exploring. (csic.es)
  • RNA editing is essential for the normal development of plant and is involved in a wide variety of biological pathways. (biomedcentral.com)
  • The authors noted that mouse models of Rett syndrome "are ideally suited to test the efficacy of programmable RNA editing in vivo. (genengnews.com)
  • They asked three questions: Is it possible to edit MeCP2 RNA in several different types of neurons in adult mice in vivo? (genengnews.com)
  • The study demonstrated that, in an in vivo research model of Hurler syndrome, treatment with the Axiomer® EONs resulted in editing of RNA and partial restoration of the enzymatic activity that is missing in this syndrome. (pharmiweb.com)
  • During our experiments, evidence suggested that the primary target of ZαADAR1 in vivo is RNA rather than DNA. (ntu.edu.sg)
  • Previous studies of the specificity of CBEs have identified off-target DNA edits in mammalian cells 5,6 . (massgeneral.org)
  • Cells were sorted directly into GenElute™ Mammalian RNA Extraction Kit Lysis Buffer (Product No. RTN10 , component No. L8265 ), frozen and stored at -70°C until extraction. (sigmaaldrich.com)
  • Total RNA was extracted from 10-, 100-, and 1000-cell samples using the GenElute Mammalian RNA Isolation kit. (sigmaaldrich.com)
  • RNA Isolation and Characterization Protocols offers biological investigators a powerful and highly useful collection of up-to-date methods for the isolation of RNA from a variety of sources, including bacterial, plant, and mammalian cells. (abebooks.com)
  • Her research group and others in the editing field also want to learn more about how to increase editing efficiency while diminishing off-target effects. (genengnews.com)
  • This study reveals an unexpected role of GUN1 in affecting plastid RNA-editing efficiency during retrograde signaling through interactions with MORF2 and demonstrates a potential role for MORF2 in retrograde signaling. (pnas.org)
  • Our study uncovers a role for GUN1 in the regulation of RNA-editing efficiency in damaged chloroplasts and suggests that MORF2 is involved in retrograde signaling. (pnas.org)
  • These variants also showed more precise on-target DNA editing than the wild-type CBE and, for most guide RNAs tested, no substantial reduction in editing efficiency. (massgeneral.org)
  • And while the average editing efficiency at the 17 sites was about 53 percent, it ranged from 34 percent to 68 percent across all sites and exceeded 50 percent at 11 sites, the team added. (genomeweb.com)
  • In addition, the effect of decreasing RNA input on amplification efficiency was examined. (sigmaaldrich.com)
  • RNA editing of AMPA receptor subunit GluR-B: a base-paired intron-exon structure determines position and efficiency. (semanticscholar.org)
  • Editing efficiency of a Drosophila gene correlates with a distant splice site selection. (semanticscholar.org)
  • Early experiments succeeded in creating a chimeric single guide RNA, or sgRNA, that combines the crRNA and tracrRNA into a single RNA strand rather than the duplex found in nature. (sigmaaldrich.com)
  • Not only do we specialize in transfection of RNA (siRNA, microRNA, sgRNA, crRNA:tracrRNA ) but we offer multiple reagent compositions that have proven success in specific cell lines. (horizondiscovery.com)
  • DharmaFECT 1, 2, 3 or 4 transfection reagents are specifically formulated for transfection of RNAs (siRNA, microRNA, crRNA:tracrRNA or sgRNA). (horizondiscovery.com)
  • DharmaFECT Duo transfection reagent is recommended for co-transfection of RNA (siRNA, microRNA, sgRNA or crRNA:tracrRNA) and plasmids. (horizondiscovery.com)
  • While IVT sgRNAs can elicit an immune response, synthetic sgRNA or crRNA:tracrRNA have little to no effect on the immune response and permit chemical modifications to be incorporated to the RNA for increased stability. (technologynetworks.com)
  • However, it turns out that the bases in the RNA can be changed dynamically on the fly in a fine-tuning process called RNA editing . (icr.org)
  • But until now, its effects on RNA, which contains three of the same bases as DNA, had escaped scrutiny. (sott.net)
  • Number of editing sites were 20 to 4 per 1000 bases, and no silent editing was observed. (nii.ac.jp)
  • MORF2 overexpression causes widespread RNA-editing changes and a strong genomes uncoupled ( gun ) molecular phenotype similar to gun1 . (pnas.org)
  • A Massachusetts General Hospital (MGH) research team reports that several of the recently developed CRISPR base editors, which create targeted changes in a single DNA base, can induce widespread off-target effects in RNA, extending beyond the targeted DNA. (massgeneral.org)
  • Nascent-seq indicates widespread cotranscriptional RNA editing in Drosophila. (semanticscholar.org)
  • RNA editing is an important co/post-transcriptional molecular process able to modify RNAs by nucleotide insertions/deletions or substitutions. (frontiersin.org)
  • Although plant RNA editing has been known for over two decades, the molecular mechanism is poorly understood. (cornell.edu)
  • The Frontiers in Molecular Biology series has provided a tight little volume, RNA Editing , which provides one-stop-shopping for some of the most current data available on this fascinating subject. (oup.com)
  • We were quite surprised at the number - tens of thousands - of RNA edits and the frequency of these alterations that we observed with the two classes of base editors," says lead author Julian Grünewald, MD, MGH Molecular Pathology and Harvard Medical School. (massgeneral.org)
  • RNA editing is an exciting therapeutic strategy that is rapidly evolving," said Phillip D. Zamore, PhD, a Howard Hughes Medical Institute Investigator, Gretchen Stone Cook Chair of Biomedical Sciences, Professor of Biochemistry and Molecular Pharmacology, and Chair of the RNA Therapeutics Institute at the University of Massachusetts Medical School. (pharmiweb.com)
  • Axiomer® EONS mediate single nucleotide changes to RNA in a highly specific and targeted way using molecular machinery that is present in human cells. (pharmiweb.com)
  • In this regard the nomenclature is apt: in general, splicing is a cut-and-paste mechanism and editing is one of fine-tuning. (pubmedcentralcanada.ca)
  • Mechanism of trypanosome RNA editing. (embopress.org)
  • To exploit the vast potential of microbes, scientists must be able to precisely edit their genetic information. (eurekalert.org)
  • Davidson's lab now is using the genetic tools from this study to illuminate further the role of RNA editing during development, where it is implicated in regulation of growth. (asbmb.org)
  • Very recently, we and others have started to develop tools that allow to reprogram the genetic information at the RNA level by a process called site-directed RNA editing. (europa.eu)
  • In contrast to CRISPR-Cas gene-editing nucleases, which induce targeted double-strand DNA breaks in order to make genetic changes, CRISPR base editors are able to change a single nucleotide in a DNA strand without inducing such breaks. (massgeneral.org)
  • many genetic diseases are caused by problems with RNA, a working copy of DNA that is translated into proteins. (salk.edu)
  • The new Salk tool, called CasRx, opens up the vast potential of RNA and proteins to genetic engineering, giving researchers a powerful way to develop new gene therapies as well as investigate fundamental biological functions. (salk.edu)
  • ProQR is pioneering a next-generation RNA technology called Axiomer®, which could potentially yield a new class of medicines for genetic diseases. (pharmiweb.com)
  • ProQR Therapeutics is dedicated to changing lives through the creation of transformative RNA medicines for the treatment of severe genetic rare diseases such as cystic fibrosis, Leber's congenital amaurosis 10 and dystrophic epidermolysis bullosa. (pharmiweb.com)
  • We began the project with the hypothesis that different CRISPR systems may have been specialized throughout an evolutionary arms race between bacteria and their viruses, potentially giving them the ability to target viral RNA," explains Salk Research Associate Silvana Konermann, an HHMI Hanna Gray Fellow and the paper's first author. (salk.edu)
  • Compared to other technologies that target RNA, CasRx is unique due to its small size (making it easier to package into therapeutically relevant viral vectors), its high degree of effectiveness, and the fact that it created no discernible off-target effects compared to RNA interference. (salk.edu)
  • The antiviral effects are due to hyper-editing and mutagenesis of viral RNAs ( Samuel, 2011 ). (elifesciences.org)
  • It can affect the activity, localization as well as stability of RNAs, and has been linked with human diseases. (wikipedia.org)
  • Thus, understanding how the process of RNA-editing is regulated has important implications for human health. (biomedcentral.com)
  • CasRx (magenta) targeting RNA in the nucleus of human cells (gray). (salk.edu)
  • The authors conducted pioneering studies to reveal that RNA editing modulates drug metabolism potencies in the human liver, as well as the response of cancer cells to chemotherapy agents. (ovid.com)
  • We will analyze human specific RNA editing and determine their role in brain function. (neurodegenerationresearch.eu)
  • 2004) Systematic identification of abundant A-to-I editing sites in the human transcriptome. (oalib.com)
  • Several binding sites were conserved between E. coli and human ribosomes, revealing that formation of Z-like RNA conformations might be a conserved property of the dynamic ribosome structure during translation. (ntu.edu.sg)
  • While RNA interference has proven useful for manipulating gene regulation in certain organisms, there has been a strong motivation to develop an orthogonal nucleic-acid-based RNA-recognition system such as RCas9," Doudna says. (eurekalert.org)
  • A recent paper by Davidson and colleagues, published in RNA Journal, deepens our understanding of tissue-specific regulation of programmed alteration of RNA, known as RNA editing, in the intestine and the liver. (asbmb.org)
  • In addition to increasing our knowledge of the regulation of plant organellar RNA editing under stress conditions, this research uncovers a possible link between retrograde signaling and plastid RNA editing. (pnas.org)
  • 2008. Gene regulation by SINES and inosines: biological consequences of A-to-I editing of Alu element inverted repeats. (icr.org)
  • However, at present, very little is known about the regulation of editing across tissues, and individuals. (biomedcentral.com)
  • Finally, we want to continue our analysis on the role of RNA editing in the regulation of the GABA-A receptor during brain development. (neurodegenerationresearch.eu)
  • To identify RNA editing sites, we used gDNA and cDNA from seven different tissues (cerebellum, frontal lobe, corpus callosum, diencephalon, small intestine, kidney, and adrenal), all derived from a single individual so as to rule out polymorphisms among populations. (sciencemag.org)
  • Editing levels are lower in other tissues. (wikipedia.org)
  • Here, we show that cardiovascular tissues in humans and mice show massive editing and that FLNA RNA is the most prominent substrate. (medworm.com)
  • Here we present an analysis of RNA-editing patterns from 9 different tissues harvested from a single mouse. (biomedcentral.com)
  • There exists a small but remarkable amount of editing which is tissue-specific, despite comparable expression levels of the edit site across multiple tissues. (biomedcentral.com)
  • AZIN1 editing levels were significantly higher in cancer tissues at all stages (I thru IV) compared with normal mucosa. (aacrjournals.org)
  • Additionally, AZIN1 was highly edited in colorectal adenoma tissues compared to adjacent normal mucosa, suggesting this epigenetic event to be critical in normal-adenoma-carcinoma cascade. (aacrjournals.org)
  • After processing, RNA editing sites were annotated and quantified between locations (macula versus periphery) and tissues (R versus RPCS). (arvojournals.org)
  • Because A-to-I editing may affect base-pairing and RNA structure, processes including translation, splicing, RNA replication, and miR and siRNA silencing may be affected. (springer.com)
  • Now we know that RNA messages can be altered by a variety of mechanisms, and a new study in squid genetics has vaulted one of these processes-called RNA editing -to an unprecedented level of biocomplexity. (icr.org)
  • The demonstration of RNA editing in prokaryotes may only be a matter of time, considering the range of species in which the various RNA editing processes have been found. (morebooks.de)
  • Most of the RNA editing processes, however, appear to be evolutionarily recent acquisitions that arose independently. (morebooks.de)
  • The unique subset of primate editome also illuminates the general functions of RNA editing by connecting it to particular gene regulatory processes, based on the characterized outcome of a gene regulatory level in different individuals or primate species with or without these editing events. (springer.com)
  • Although much remains unknown, a picture of highly organized complexes is emerging that shows that the complex that catalyzes the central steps of editing is partitioned into distinct insertion and deletion editing subcomplexes. (nih.gov)
  • Deletion of Rbm47, but not A1cf, caused a large, tissue-specific change in the RNA editing profile, with the intestines being most affected. (asbmb.org)
  • unligated RNAs cleaved at U‐deletion sites accumulated. (embopress.org)
  • Thus band IV ligase is needed to seal RNAs in U‐deletion. (embopress.org)
  • In addition to the incredible variability achieved with alternative splicing, it has also been discovered that another form of dynamic RNA alteration exists called RNA editing. (icr.org)
  • Whereas haloperidol, a typical antipsychotic drug that is primarily a dopamine receptor antagonist, reduced 5-HT2C VNV isoform frequency and the level of RNA editing at the D site, risperidone and not the prototype atypical antipsychotic drug clozapine increased the frequency of 5-HT2C VNV and D-site editing. (ox.ac.uk)