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*  RNA as a Drug Target: Recent Patents on the Catalytic Activity of Trans- Splicing Ribozymes Derived from Group I Intron RNA |...
Title: RNA as a Drug Target: Recent Patents on the Catalytic Activity of Trans- Splicing Ribozymes Derived from Group I Intron RNA. VOLUME: 4 ISSUE: 1. Author(s):Irudayam Maria Johnson. Affiliation:Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.. Keywords:Group I intron ribozyme therapy, group I intron splicing inhibitors, trans splicing ribozyme, patents of trans splicing ribozymes, drug targeting, small molecules, self-splicing, catalytic activity, RNA repair, mutant RNA. Abstract: The importance of RNA in vital cellular events like gene expression, transport, self-splicing catalytic activity etc., renders them an alternative target for drugs and other specific RNA binding ligands. RNA targets gain significance for the fact that targeting DNA with therapeutics sooner leads to drug resistance and severe side effects by ...
http://www.eurekaselect.com/93705/article/rna-drug-target-recent-patents-catalytic-activity-trans-splicing-ribozymes-derived
*  RNApathwaysDB - a database of RNA maturation and decay.
Non-catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved ...
http://www.genesilico.pl/rnapathwaysdb/proteins/71/
*  Interferon Action: Inhibition of Vesicular Stomatitis Virus RNA Synthesis Induced by Virion-Bound Polymerase | Science
The particle-bound RNA polymerase activity of vesicular stomatitis virus (VSV) can be demonstrated in vivo. Linear synthesis of viral RNA persists for 5 to 6 hours at 34°C in infected monolayers of chick embryo cells treated with cycloheximide and actinomycin D to block synthesis of protein and cell-specific RNA. At least 55 percent of the RNA made under these conditions is complementary to virion RNA. RNA synthesis mediated by VSV polymerase activity is inhibited in cells first treated with chick-derived interferon or polyriboinosinate• polyribocytidylate, but not by mouse interferon. The RNA product of VSV polymerase activity is present throughout the cytoplasm, and its synthesis is inhibited by the interferon system, as judged by autoradiographs that show the physical distribution, in cells, of RNA produced by virion polymerase in the absence of translation-a ...
http://science.sciencemag.org/content/174/4009/593
*  Solid-phase synthesis and thermal denaturation study of cyclic PNAs targeting the HIV-1 TAR RNA loop. - Semantic Scholar
Cyclic PNAs targeting the HIV-1 TAR RNA loop have been synthesized following a convenient solid-phase strategy which allows on-resin cyclisation. UV-monitored thermal denaturation studies demonstrate that these cyclic PNAs are able to strongly interact with their TAR RNA target, very likely through the formation of a six-base pair stable complex, involving the TAR RNA loop.
https://www.semanticscholar.org/paper/Solid-phase-synthesis-and-thermal-denaturation-stu-Upert-Mehiri/5b1e939e01bfd7a7dff76085bb9c8b076c9fcf44
*  Probabilistic context-free grammars for classification of helix-helix contact sites and recognition of amyloidogenic peptides
Hidden Markov Models power many state-of-the-art tools in the field of protein bioinformatics. While excelling in their tasks, these methods of protein analysis do not convey directly information on medium and long-range residue-residue interactions. This requires an expressive power of at least context-free grammars. However, application of more powerful grammar formalisms to protein analysis has been surprisingly limited. We have developed a probabilistic grammatical framework for problem-specific protein languages, which has been already successfully applied to recognition of ligand binding sites. The core of the model consists of a probabilistic context-free grammar (PCFG), automatically inferred by a genetic algorithm from only a generic set of expert-based rules and positive training sequences. Here, we show that the PCFG approach matches state-of-the-art performance in two other tasks: classification of transmembrane helix-helix pairs and recognition of amyloidogenic peptides. First, the
https://hal.inria.fr/hal-00937763
*  The human cap-binding complex is functionally connected to the nuclear RNA exosome - Radcliffe Department of Medicine
Nuclear processing and quality control of eukaryotic RNA is mediated by the RNA exosome, which is regulated by accessory factors. However, the mechanism of exosome recruitment to its ribonucleoprotein (RNP) targets remains poorly understood. Here we report a physical link between the human exosome and the cap-binding complex (CBC). The CBC associates with the ARS2 protein to form CBC-ARS2 (CBCA) and then further connects, together with the ZC3H18 protein, to the nuclear exosome targeting (NEXT) complex, thus forming CBC-NEXT (CBCN). RNA immunoprecipitation using CBCN factors as well as the analysis of combinatorial depletion of CBCN and exosome components underscore the functional relevance of CBC-exosome bridging at the level of target RNA. Specifically, CBCA suppresses read-through products of several RNA families by promoting their transcriptional termination. We suggest that the RNP 5′ cap links transcription termination ...
https://www.rdm.ox.ac.uk/publications/550346
*  Vault RNA - Wikipedia
Many eukaryotic cells contain large ribonucleoprotein particles in the cytoplasm known as vaults. The vault complex comprises the major vault protein (MVP), two minor vault proteins (VPARP and TEP1), and a variety of small untranslated RNA molecules. Given the association with the nuclear membrane and the location within the cell, vaults are thought to play roles in intracellular and nucleocytoplasmic transport processes. Also, given that the structure and protein composition are highly conserved among species, it is believed that the roles vault plays are integral to eukaryotic function. While vault proteins appear to be present in a variety of organisms, vaults isolated from higher eukaryotes contain a small portion, about 5%, of small untranslated RNAs called vault RNAs, or vtRNAs. These RNA molecules are polymerase III transcripts. In addition, a study, using cryo-electron microscopy, has determined that ...
https://en.wikipedia.org/wiki/Vault_RNA
*  Pseudoknot - Wikipedia
A pseudoknot is a nucleic acid secondary structure containing at least two stem-loop structures in which half of one stem is intercalated between the two halves of another stem. The pseudoknot was first recognized in the turnip yellow mosaic virus in 1982. Pseudoknots fold into knot-shaped three-dimensional conformations but are not true topological knots. The structural configuration of pseudoknots does not lend itself well to bio-computational detection due to its context-sensitivity or "overlapping" nature. The base pairing in pseudoknots is not well nested; that is, base pairs occur that "overlap" one another in sequence position. This makes the presence of pseudoknots in RNA sequences more difficult to predict by the standard method of dynamic programming, which use a recursive scoring system to identify paired stems and consequently, most cannot detect non-nested base pairs. The newer method of stochastic context-free grammars suffers from the same problem. Thus, popular secondary ...
https://en.wikipedia.org/wiki/Pseudoknot
*  Hog1 bypasses stress-mediated down-regulation of transcription by RNA polymerase II redistribution and chromatin remodeling
Cells are subjected to dramatic changes of gene expression upon environmental changes. Stresscauses a general down-regulation of gene expression together with the induction of a set of stress-responsivegenes. The p38-related stress-activated protein kinase Hog1 is an important regulator of transcription uponosmostress in yeast. Genome-wide localization studies of RNA polymerase II (RNA Pol II) and Hog1 showed that stress induced major changes in RNA Pol II localization, with a shift toward stress-responsive genes relative to housekeeping genes. RNA Pol II relocalization required Hog1, which was also localized to stress-responsive loci. In addition to RNA Pol II-bound genes, Hog1 also localized to RNA polymerase III-bound genes, pointing to a wider role for Hog1 in transcriptional control than initially expected. Interestingly, an increasing association of Hog1 with stressresponsive genes was strongly ...
http://www.recercat.cat/handle/2072/220690
*  The formation of mitochondrial ribonucleoprotein complexes involving guide RNA molecules in Trypanosoma brucei. - TUbiblio
Transcripts from mitochondrial (maxicircle) genes of kinetoplastid organisms undergo RNA editing characterized by a series of reactions that insert and delete uridine nucleotides within the sequence of the pre-mRNAs. Guide RNAs, which complement fully edited mRNAs, provide the information for the edited sequence by an unknown mechanism. We report here that guide RNA molecules associate with other mitochondrial components to form four specific, stable ribonucleoprotein complexes. The complexes form very rapidly at a low monovalent cation concentration, and their formation is blocked by heparin or pretreatment of the mitochondrial lysate with SDS. ATP hydrolysis is not required but slightly stimulates complex association up to concentrations of 5 mM. The results are suggestive of a sequential assembly of the ribonucleoprotein complexes, and their possible involvement during the kinetoplastid RNA editing is ...
http://tubiblio.ulb.tu-darmstadt.de/54924/
*  "A sequence-specific RNA binding complex expressed in murine germ cells" by H G. Davies, F Giorgini et al.
The protamine mRNAs are stored for up to 8 days as translationally repressed ribonucleoprotein particles during murine spermatogenesis. Translational repression of the protamine 1, Prm1, mRNA is controlled by sequences in its 3'-untranslated region (UTR). In this study we used the yeast three-hybrid system to clone Msy4, which encodes a novel member of the Y box family of nucleic acid binding proteins. MSY4 specifically binds to a site within the 5' most 37 nucleotides in the Prm1 3' UTR. Msy4 is highly expressed in the testis, and the protein is detected in the cytoplasm of germ cells in both the testis and the ovary, where repressed messages are stored. Analysis of a previously described 48/50-kDa binding activity in testis extracts by electrophoretic mobility shift assays and immunoprecipitation indicates the activity is composed of MSY4 and MSY2, another mouse Y box protein. Polysome analysis demonstrates MSY4 is associated with mRNPs, consistent with MSY4 ...
https://mouseion.jax.org/stfb2000_2009/854/
*  Presence of angiotensinogen messenger RNA in various cultured cell lines. | Hypertension
The presence of angiotensinogen messenger RNA (mRNA) was assessed in total RNA extracted from hepatoma, glioma, neuroblastoma, and glioma-neuroblastoma hybrid cell lines. Total RNA from 1 X 10(7) cells was extracted, transferred to a membrane, and hybridized with a 32P-labeled, full-length (1650-base pair) rat angiotensinogen complementary DNA (cDNA). Angiotensinogen RNA sequences could be definitively detected only in hepatoma cells. Steroids were used in an attempt to increase the angiotensinogen mRNA level. Dexamethasone (2 X 10(-6) M) or 17 beta-estradiol (1 X 10(-7) M) was added to the cultures 18 to 24 hours prior to harvest. Dexamethasone treatment of the hepatoma cells resulted in a large increase in angiotensinogen mRNA, whereas estradiol had no effect. Steroids failed to induce detectable levels of angiotensinogen mRNA in total RNA from the other ...
http://hyper.ahajournals.org/content/9/6_Pt_2/III25
*  Probing stability, specificity, and modular structure in group I intron RNAs
Many functional RNAs are required to fold into specific three-dimensional structures. A fundamental property of RNA is that its secondary structure and even some tertiary contacts are highly stable, which gives rise to independent modular RNA motifs and makes RNAs prone to adopting misfolded intermediates. Consequently, in addition to stabilizing the native structure relative to the unfolded species (defined here as stability), RNAs are faced with the challenge of stabilizing the native structure relative to alternative structures (defined as structural specificity). How RNAs have evolved to overcome these challenges is incompletely understood. Self-splicing group I introns have been used to study RNA structure and folding for decades. Among them, the Tetrahymena intron was the first discovered and has been studied extensively. In this work, we found that a version of the ...
https://repositories.lib.utexas.edu/handle/2152/ETD-UT-2010-12-2198
*  Molecular genetics of telomeres and telomerase | Department of Biology
The mechanism of telomere elongation by telomerase. In this example the telomerase enzyme is synthesizing the repeated sequence TTGGGG, which is the telomeric sequence of Tetrahymena thermophila.. The first detection of telomerase activity, in the ciliateTetrahymena thermophila, was followed by its detection in a variety of organisms including vertebrates, yeast, and plants. In the absence of telomerase activity, telomeres shorten with each cell division. Normal human somatic cells lack detectable telomerase activity, whereas telomerase is activated in germ cells, immortalized cells and the majority of primary tumors. The correlation between telomerase activity and tumor growth has spurred investigations of the possiblities to use telomerase activity as a target for anticancer drug treatments.. Our identification of much longer telomeric repeat units (16-26 bp) in several yeast species has expanded the previous range of telomeric repeat sequences to include not only more complex sequences, but ...
https://www.biology.lu.se/research/research-groups/genetics-telomeres-and-telomerase/molecular-genetics-of-telomeres-and-telomerase
*  Modomics - A Database of RNA Modifications
To characterize the substrate specificity of the putative RNA:pseudouridine (Psi)-synthase encoded by the Saccharomyces cerevisiae open reading frame (ORF) YGR169c, the corresponding gene was deleted in yeast, and the consequences of the deletion on tRNA and small nuclear RNA modification were tested. The resulting DeltaYGR169c strain showed no detectable growth phenotype, and the only difference in Psi formation in stable cellular RNAs was the absence of Psi at position 31 in cytoplasmic and mitochondrial tRNAs. Complementation of the DeltaYGR169c strain by a plasmid bearing the wild-type YGR169c ORF restored Psi(31) formation in tRNA, whereas a point mutation of the enzyme active site (Asp(168)--,Ala) abolished tRNA:Psi(31)-synthase activity. Moreover, recombinant His(6)-tagged Ygr169 protein produced in Escherichia coli was capable of forming Psi(31) in vitro using tRNAs ...
http://modomics.genesilico.pl/papers/198/
*  Detection and quantification of hippocampal synaptophysin messenger RNA in schizophrenia using autoclaved, formalin-fixed,...
Most in situ hybridization histochemistry studies of messenger RNA in human brain have been carried out on frozen tissue. Recently, autoclaving has been reported to enable routinely processsed material to be used for in situ localization of messenger RNA. We have investigated whether autoclaving also permits in situ hybridization histochemistry to be used quantitatively. To do this, we targeted synaptophysin messenger RNA with a 35S-labelled oligonucleotide probe in autoclaved, formalin-fixed, paraffin wax-embedded sections of the hippocampal formation of 11 schizophrenics and 11 controls. We compared the results with those seen on frozen sections from adjacent blocks, which had been used previously to demonstrate a loss of the messenger RNA in schizophrenia. Synaptophysin messenger RNA was readily detected in the autoclaved sections. The hybridization signal correlated strongly with that seen in the frozen sections. We ...
https://www.neuroscience.ox.ac.uk/publications/657604
*  A comprehensive comparison of comparative RNA structure prediction approaches | BMC Bioinformatics | Full Text
While the plans A, B and C we are about to evaluate strive to find a good consensus structure from sequence data, the "truth" available to us comes in a different form. Structural databases only convey a consensus by example: They provide a reference sequence, say B1, with an experimentally proved structure S1, and provide a multiple sequence alignment of B1, S1 and additional sequences B2,..., B n in the family under consideration. The sequence alignment is chosen to exhibit structural similarities between the reference structure and the other family members, but in general, we do not know the precise model of achieving similarity, nor do we know whether this model has been solved to optimality.. One consequence of this situation would be to conclude that the reference structure is the only reliable anchor point available to us for evaluation. Comparative analysis tools would then be evaluated by the capacity to predict this particular structure by using family information. This would be a ...
https://bmcbioinformatics.biomedcentral.com/articles/10.1186/1471-2105-5-140
*  New RNA Researcher Joins OSU | The Center for RNA Biology
Guramrit Singh grew up in northern India in the state of Panjab - the land of five (panj) rivers (aab). His fascination with biology (microbes in particular) led him to pursue an undergraduate degree (B.Sc. Industrial Microbiology, 1998) at Guru Nanak Dev University, Amritsar. It was here that he first discovered the world of molecular and cellular biology, and developed a deep-rooted interest in this general subject area that has guided all subsequent pursuits in his education and research career. Guramrit got the first taste of molecular biology research while pursuing a Masters degree (M.Sc. Biotechnology, 2000) at Madurai Kamaraj University, Tamil Nadu, and then as a Junior Research Fellow at the Indian Institute of Science, Bangalore. In 2001, he shifted to the United States for his graduate studies at University of Colorado, Boulder. Guramrit's doctoral thesis work in Dr. Jens Lykke-Andersen's lab on nonsense-mediated mRNA degradation pathway in human cells (Ph.D., 2007) marked the ...
http://rna.osu.edu/2013/07/12/new-rna-researcher-joins-osu-2/
*  Apple miRNAs and tasiRNAs with novel regulatory networks | Genome Biology | Full Text
MicroRNAs (miRNAs) and their regulatory functions have been extensively characterized in model species but whether apple has evolved similar or unique regulatory features remains unknown. We performed deep small RNA-seq and identified 23 conserved, 10 less-conserved and 42 apple-specific miRNAs or families with distinct expression patterns. The identified miRNAs target 118 genes representing a wide range of enzymatic and regulatory activities. Apple also conserves two TAS gene families with similar but unique trans-acting small interfering RNA (tasiRNA) biogenesis profiles and target specificities. Importantly, we found that miR159, miR828 and miR858 can collectively target up to 81 MYB genes potentially involved in diverse aspects of plant growth and development. These miRNA target sites are differentially conserved among MYBs, which is largely influenced by the location ...
https://genomebiology.biomedcentral.com/articles/10.1186/gb-2012-13-6-r47
*  Faculty Research Page | Department of Molecular & Cell Biology
Wu RA, Dagdas YS, Yilmaz ST, Yildiz A, Collins K. Single-molecule imaging of telomerase reverse transcriptase in human telomerase holoenzyme and minimal RNP complexes. eLife in press (2015).. Hockemeyer D, Collins K. Control of human telomerase action at telomeres. NSMB in press (2015).. Vogan JM, Collins K. Dynamics of human telomerase holoenzyme assembly and subunit exchange across the cell cycle. JBC 290: 21320-35 (2015).. Upton HE, Hong K, Collins K.Direct single-stranded DNA binding by Teb1 mediates the recruitment of Tetrahymena telomerase to telomeres. MCB 34: 4200-12 (2014).. Wu RA, Collins K. Sequence specificity of human telomerase. PNAS 111: 11234-5 (2014).. Sexton AN, Regalado SG, Lai CS, Cost GJ, O'Neil CM, Urnov FD, Gregory PD, Jaenisch R, Collins K, Hockemeyer D. Genetic and molecular identification of three human TPP1 functions in telomerase action: Recruitment, activation, and homeostasis set-point regulation. Genes Dev. 28: 1885-99 (2014).. Katibah GE, Qin Y, Sidote DJ, Yao J, ...
https://mcb.berkeley.edu/faculty/bbs/collinsk.html
*  Putative pre-mRNA-splicing factor ATP-dependent RNA helicase DHX32
DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a member of this family. The function of this member has not been determined. Alternative splicing of this gene generates 2 transcript variants, but the full length nature of one of the variants has not been defined. [provided by RefSeq, Jul 2008 ...
https://pharos.nih.gov/idg/targets/Q7L7V1
*  Rnaclubzurich:Projects - OpenWetWare
By means of DNA microarrays we aim at determining the RNA targets of yeast RBPs that associate with ribosomes and are thus prime candidates to specifically regulate mRNA translation. Our investigations have focused on two evolutionary conserved La-motif (LM) containing proteins from the yeast Saccharomyces cerevisiae, termed Slf1p and Sro9p. These proteins had previously been shown to bind RNA homopolymers in vitro and to preferentially associate with polysomes (Sobel & Wolin, 1999). We found that the two proteins bind to a largely overlapping set of hundreds of mRNAs. In contrast to the bona fide La protein, which binds to the 3'polyuridine tail of nascent RNA polymerase III transcripts, we could not find significant association of noncoding RNAs with Sro9p and Slf1p. This is in agreement with the fact that Slf1p and Sro9p are mainly cytoplasmic whereas La proteins are primarily localized in the nucleus. We ...
https://openwetware.org/wiki/?title=Rnaclubzurich:Projects&oldid=282189
*  Primary transcript - Wikipedia
A primary transcript is the single-stranded ribonucleic acid (RNA) product synthesized by transcription of DNA, and processed to yield various mature RNA products such as mRNAs, tRNAs, and rRNAs. The primary transcripts designated to be mRNAs are modified in preparation for translation. For example, a precursor messenger RNA (pre-mRNA) is a type of primary transcript that becomes a messenger RNA (mRNA) after processing. There are several steps contributing to the production of primary transcripts. All these steps involve a series of interactions to initiate and complete the transcription of DNA in the nucleus of eukaryotes. Certain factors play key roles in the activation and inhibition of transcription, where they regulate primary transcript production. Transcription produces primary transcripts that are further modified by several ...
https://en.wikipedia.org/wiki/Primary_transcript
*  The Role of Circular RNAs in Molecular Biology of the Brain | babs
Our research focuses on studying brain transcriptome using next-generation sequencing, in particular, RNA-Seq technique. We are interested in region-specific gene expression profiles in brain development and ageing as well as perturbation of the transcriptome as a result of neurodegeneration.. Recent advances in genomic technology allowed to uncover new RNA species, circular RNAs (circRNAs; Fig. 1). CircRNAs have been identified as a naturally occurring family of widespread and diverse endogenous noncoding RNAs that may regulate gene expression in mammals (Huang et al. 2017) and are perturbed as a result of neurodegeneration (Chen et al. 2016). They are unusually stable RNA molecules with cell type- or developmental stage-specific expression patterns. However, the role of circRNAs in molecular biology of the brain remains unknown. Hence, the aim of this project is to ...
https://www.babs.unsw.edu.au/research/role-circular-rnas-molecular-biology-brain
*  Ribonuclease bound to transfer RNA - Stock Image C008/8444 - Science Photo Library
Ribonuclease bound to transfer RNA. Computer model showing the molecular structure of a ribonuclease Z (RNase Z, blue) enzyme bound to a transfer RNA (tRNA) molecule (red). RNase is a type of nuclease that catalyses the degradation of RNA (ribonucleic acid) into smaller components in preparation for other genetic processes. tRNA is RNA that transfers a specific active amino acid to a growing polypeptide chain at the site of protein synthesis during gene translation. RNase Z causes conformational changes in both molecules to promote reorganization of the catalytic site and tRNA cleavage. - Stock Image C008/8444
http://www.sciencephoto.com/media/390150/view