Alu Elements: The Alu sequence family (named for the restriction endonuclease cleavage enzyme Alu I) is the most highly repeated interspersed repeat element in humans (over a million copies). It is derived from the 7SL RNA component of the SIGNAL RECOGNITION PARTICLE and contains an RNA polymerase III promoter. Transposition of this element into coding and regulatory regions of genes is responsible for many heritable diseases.Repetitive Sequences, Nucleic Acid: Sequences of DNA or RNA that occur in multiple copies. There are several types: INTERSPERSED REPETITIVE SEQUENCES are copies of transposable elements (DNA TRANSPOSABLE ELEMENTS or RETROELEMENTS) dispersed throughout the genome. TERMINAL REPEAT SEQUENCES flank both ends of another sequence, for example, the long terminal repeats (LTRs) on RETROVIRUSES. Variations may be direct repeats, those occurring in the same direction, or inverted repeats, those opposite to each other in direction. TANDEM REPEAT SEQUENCES are copies which lie adjacent to each other, direct or inverted (INVERTED REPEAT SEQUENCES).Long Interspersed Nucleotide Elements: Highly repeated sequences, 6K-8K base pairs in length, which contain RNA polymerase II promoters. They also have an open reading frame that is related to the reverse transcriptase of retroviruses but they do not contain LTRs (long terminal repeats). Copies of the LINE 1 (L1) family form about 15% of the human genome. The jockey elements of Drosophila are LINEs.Short Interspersed Nucleotide Elements: Highly repeated sequences, 100-300 bases long, which contain RNA polymerase III promoters. The primate Alu (ALU ELEMENTS) and the rodent B1 SINEs are derived from 7SL RNA, the RNA component of the signal recognition particle. Most other SINEs are derived from tRNAs including the MIRs (mammalian-wide interspersed repeats).DNA Transposable Elements: Discrete segments of DNA which can excise and reintegrate to another site in the genome. Most are inactive, i.e., have not been found to exist outside the integrated state. DNA transposable elements include bacterial IS (insertion sequence) elements, Tn elements, the maize controlling elements Ac and Ds, Drosophila P, gypsy, and pogo elements, the human Tigger elements and the Tc and mariner elements which are found throughout the animal kingdom.Genome, Human: The complete genetic complement contained in the DNA of a set of CHROMOSOMES in a HUMAN. The length of the human genome is about 3 billion base pairs.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Molecular Sequence Data: 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.PrimatesRetroelements: Elements that are transcribed into RNA, reverse-transcribed into DNA and then inserted into a new site in the genome. Long terminal repeats (LTRs) similar to those from retroviruses are contained in retrotransposons and retrovirus-like elements. Retroposons, such as LONG INTERSPERSED NUCLEOTIDE ELEMENTS and SHORT INTERSPERSED NUCLEOTIDE ELEMENTS do not contain LTRs.Strepsirhini: A suborder of PRIMATES consisting of the following five families: CHEIROGALEIDAE; Daubentoniidae; Indriidae; LEMURIDAE; and LORISIDAE.Sequence Homology, Nucleic Acid: 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.Exons: 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.3' Flanking Region: The region of DNA which borders the 3' end of a transcription unit and where a variety of regulatory sequences are located.Hominidae: Family of the suborder HAPLORHINI (Anthropoidea) comprising bipedal primate MAMMALS. It includes modern man (HOMO SAPIENS) and the great apes: gorillas (GORILLA GORILLA), chimpanzees (PAN PANISCUS and PAN TROGLODYTES), and orangutans (PONGO PYGMAEUS).Response Elements: Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promoter and enhancer regions.Cercopithecidae: The family of Old World monkeys and baboons consisting of two subfamilies: CERCOPITHECINAE and COLOBINAE. They are found in Africa and part of Asia.Introns: 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.RNA Editing: 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).Promoter Regions, Genetic: 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.Pan troglodytes: The common chimpanzee, a species of the genus Pan, family HOMINIDAE. It lives in Africa, primarily in the tropical rainforests. There are a number of recognized subspecies.Enhancer Elements, Genetic: Cis-acting DNA sequences which can increase transcription of genes. Enhancers can usually function in either orientation and at various distances from a promoter.Evolution, Molecular: The process of cumulative change at the level of DNA; RNA; and PROTEINS, over successive generations.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.DNA: 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).RNA Polymerase III: 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, Insertional: Mutagenesis where the mutation is caused by the introduction of foreign DNA sequences into a gene or extragenic sequence. This may occur spontaneously in vivo or be experimentally induced in vivo or in vitro. Proviral DNA insertions into or adjacent to a cellular proto-oncogene can interrupt GENETIC TRANSLATION of the coding sequences or interfere with recognition of regulatory elements and cause unregulated expression of the proto-oncogene resulting in tumor formation.Genes, Neurofibromatosis 1: Tumor suppressor genes located on the long arm of human chromosome 17 in the region 17q11.2. Mutation of these genes is thought to cause NEUROFIBROMATOSIS 1, Watson syndrome, and LEOPARD syndrome.Gorilla gorilla: This single species of Gorilla, which is a member of the HOMINIDAE family, is the largest and most powerful of the PRIMATES. It is distributed in isolated scattered populations throughout forests of equatorial Africa.Regulatory Sequences, Nucleic Acid: Nucleic acid sequences involved in regulating the expression of genes.Gene Conversion: The asymmetrical segregation of genes during replication which leads to the production of non-reciprocal recombinant strands and the apparent conversion of one allele into another. Thus, e.g., the meiotic products of an Aa individual may be AAAa or aaaA instead of AAaa, i.e., the A allele has been converted into the a allele or vice versa.Inosine: A purine nucleoside that has hypoxanthine linked by the N9 nitrogen to the C1 carbon of ribose. It is an intermediate in the degradation of purines and purine nucleosides to uric acid and in pathways of purine salvage. It also occurs in the anticodon of certain transfer RNA molecules. (Dorland, 28th ed)Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Gene Expression Regulation: 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.Polymerase Chain Reaction: 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.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.Chromosome Breakage: A type of chromosomal aberration involving DNA BREAKS. Chromosome breakage can result in CHROMOSOMAL TRANSLOCATION; CHROMOSOME INVERSION; or SEQUENCE DELETION.Consensus Sequence: A theoretical representative nucleotide or amino acid sequence in which each nucleotide or amino acid is the one which occurs most frequently at that site in the different sequences which occur in nature. The phrase also refers to an actual sequence which approximates the theoretical consensus. A known CONSERVED SEQUENCE set is represented by a consensus sequence. Commonly observed supersecondary protein structures (AMINO ACID MOTIFS) are often formed by conserved sequences.Phylogeny: The relationships of groups of organisms as reflected by their genetic makeup.CpG Islands: Areas of increased density of the dinucleotide sequence cytosine--phosphate diester--guanine. They form stretches of DNA several hundred to several thousand base pairs long. In humans there are about 45,000 CpG islands, mostly found at the 5' ends of genes. They are unmethylated except for those on the inactive X chromosome and some associated with imprinted genes.HeLa Cells: 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.Genetic Variation: Genotypic differences observed among individuals in a population.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Terminal Repeat Sequences: Nucleotide sequences repeated on both the 5' and 3' ends of a sequence under consideration. For example, the hallmarks of a transposon are that it is flanked by inverted repeats on each end and the inverted repeats are flanked by direct repeats. The Delta element of Ty retrotransposons and LTRs (long terminal repeats) are examples of this concept.RNA, Messenger: 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.Restriction Mapping: Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.Chromosome Mapping: Any method used for determining the location of and relative distances between genes on a chromosome.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Gene Rearrangement: The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development.Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories for solving biological problems including manipulation of models and datasets.Trace Elements: A group of chemical elements that are needed in minute quantities for the proper growth, development, and physiology of an organism. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)

Hereditary desmoid disease in a family with a germline Alu I repeat mutation of the APC gene. (1/466)

Two families with autosomal dominantly inherited desmoid tumors have recently been shown to have germline mutations at the 3' end of the APC gene. We subsequently identified an Amish family with autosomal dominantly inherited desmoid tumors. Genetic analysis performed on one family member, a 47-year-old man with multiple desmoid tumors and no colon polyps, revealed a protein truncating mutation in the middle of the APC gene. The truncating mutation is the result of a 337-bp insertion of an Alu I sequence into codon 1526 of the APC gene. The presence of a poly(A) tail at the 3' end of the insertion suggests that the Alu I sequence was inserted by a retrotranspositional event. Germline insertions of Alu I sequences have occasionally been reported to cause other genetic diseases including type I neurofibromatosis, hereditary site-specific breast cancer (BRCA2), and hemophilia B. However, this is the first report of a germline mutation of the APC gene resulting from an Alu I insertion.  (+info)

A novel human DNA-binding protein with sequence similarity to a subfamily of redox proteins which is able to repress RNA-polymerase-III-driven transcription of the Alu-family retroposons in vitro. (2/466)

In this study we identified a novel protein which may contribute to the transcriptional inactivity of Alu retroposons in vivo. A human cDNA clone encoding this protein (ACR1) was isolated from a human expression library using South-western screening with an Alu subfragment, implicated in the regulation of Alu in vitro transcription and interacting with a HeLa nuclear protein down-regulated in adenovirus-infected cells. Bacterially expressed ACR1 is demonstrated to inhibit RNA polymerase III (Pol III)-dependent Alu transcription in vitro but showed no repression of transcription of a tRNA gene or of a reporter gene under control of a Pol II promoter. ACR1 mRNA is also found to be down-regulated in adenovirus-infected HeLa cells, consistent with a possible repressor function of the protein in vivo. ACR1 is mainly (but not exclusively) located in cytoplasm and appears to be a member of a weakly characterized redox protein family having a central, highly conserved sequence motif, PGAFTPXCXXXXLP. One member of the family identified earlier as peroxisomal membrane protein (PMP)20 is known to interact in a sequence-specific manner with a yeast homolog of mammalian cyclosporin-A-binding protein cyclophilin, and mammalian cyclophilin A (an abundant ubiquitously expressed protein) is known to interact with human transcriptional repressor YY1, which is a major sequence-specific Alu-binding protein in human cells. It appears, therefore, that transcriptional silencing of Alu in vivo is a result of complex interactions of many proteins which bind to its Pol III promoter.  (+info)

Translational control of specific genes during differentiation of HL-60 cells. (3/466)

Eukaryotic gene expression can be regulated through selective translation of specific mRNA species. Nevertheless, the limited number of known examples hampers the identification of common mechanisms that regulate translation of specific groups of genes in mammalian cells. We developed a method to identify translationally regulated genes. This method was used to examine the regulation of protein synthesis in HL-60 cells undergoing monocytic differentiation. A partial screening of cellular mRNAs identified five mRNAs whose translation was specifically inhibited and five others that were activated as was indicated by their mobilization onto polysomes. The specifically inhibited mRNAs encoded ribosomal proteins, identified as members of the 5'-terminal oligopyrimidine tract mRNA family. Most of the activated transcripts represented uncharacterized genes. The most actively mobilized transcript (termed TA-40) was an untranslated 1.3-kilobase polyadenylated RNA with unusual structural features, including two Alu-like elements. Following differentiation, a significant change in the cytoplasmic distribution of Alu-containing mRNAs was observed, namely, the enhancement of Alu-containing mRNAs in the polysomes. Our findings support the notion that protein synthesis is regulated during differentiation of HL-60 cells by both global and gene-specific mechanisms and that Alu-like sequences within cytoplasmic mRNAs are involved in such specific regulation.  (+info)

Human-specific insertion/deletion polymorphisms in Indian populations and their possible evolutionary implications. (4/466)

DNA samples from 396 unrelated individuals belonging to 14 ethnic populations of India, inhabiting various geographical locations and occupying various positions in the socio-cultural hierarchy, were analysed in respect of 8 human-specific polymorphic insertion/deletion loci. All loci, except Alu CD4, were found to be highly polymorphic in all populations. The levels of average heterozygosities were found to be very high in all populations and, in most populations, also higher than those predicted by the island model of population structure. The coefficient of gene differentiation among Indian populations was found to be higher than populations in most other global regions, except Africa. These results are discussed in the light of two possible scenarios of evolution of Indian populations in the broader context of human evolution.  (+info)

Y chromosomal polymorphisms reveal founding lineages in the Finns and the Saami. (5/466)

Y chromosomal polymorphisms were studied in 502 males from 16 Eurasian ethnic groups including the Finns, Saami (Inari Lake area and Skolt Saami), Karelians, Mari, Mokshas, Erzas, Hungarians (Budapest area and Csangos), Khanty, Mansi, Yakuts, Koryaks, Nivkhs, Mongolians, and Latvians. The samples were analysed for polymorphisms in the Y chromosome specific Alu insertion (YAP) and six microsatellites (DYS19, DYS389-I and II, DYS390, DYS392, DYS393). The populations were also screened for the recently described Tat polymorphism. The incidence of YAP+ type was highest in the Csangos and in other Hungarians (37.5% and 17.5%, respectively). In the Karelians and the Latvians it was present at approximately the same level as commonly found in other European populations, whilst absent in our further samples of Eurasian populations, including the Finns and the Saami. Aside from the Hungarians, the C allele of the Tat polymorphism was common in all the Finno-Ugric speaking populations (from 8.2% to 63.2%), with highest incidence in the Ob-Ugrian Khanty. The C allele was also found in the Latvians (29.4%). The haplotypes found associated with the Tat C allele showed consistently lower density than those associated with the T allele, indicating that the T allele is the original form. The computation of the age of the Tat C suggested that the mutation might be a relatively recent event giving a maximum likelihood estimate of 4440 years (95% confidence interval about 3140-6200 years). The distribution patterns of the 222 haplotypes found varied considerably among the populations. In the Finns a majority of the haplotypes could be assigned to two distinct groups, one of which harboured the C allele of the Tat polymorphism, indicating dichotomous primary source of genetic variation among Finnish males. The presence of a bottleneck or founding effect in the male lineages of some of the populations, namely in the Finns and the Saami, would appear to be one likely interpretation for these findings.  (+info)

Molecular analysis of an unstable genomic region at chromosome band 11q23 reveals a disruption of the gene encoding the alpha2 subunit of platelet-activating factor acetylhydrolase (Pafah1a2) in human lymphoma. (6/466)

A region of 150 kb has been analysed around a previously isolated, lymphoma associated, translocation breakpoint located at chromosome band 11q23. This balanced and reciprocal translocation, t(11;14)(q32;q23), has been shown to result in the fusion between chromosome 11 specific sequence and the switch gamma4 region of the IGH locus. The LPC gene, encoding a novel proprotein convertase belonging to the furin family, has been identified in this region. In order to characterize further the region surrounding the translocation, we have determined the detailed structure of LPC. Here we show that LPC consists of at least 16 exons covering 25 kb, and that there is a partial duplication, involving mobile genetic elements and containing LPC exons 13-17 in a tail-tail configuration at 65 kb downstream. Since the chromosomal breakpoint lay between these two structures, the intervening region was further analysed and shown to contain at least two unrelated genes. The previously known SM22 gene was localized close to the 3' tail of LPC. Furthermore, we identified the gene encoding the alpha2 subunit of platelet-activating factor acetylhydrolase (Pafah1a2) at the chromosomal breakpoint. The position of another previously identified breakpoint was also located to within the first intron of this gene. Altogether, our results give evidence of a genomic instability of this area of 11q23 and show that Pafah1a2 and not LPC is the gene disrupted by the translocation, suggesting that deregulated Pafah1a2 may have a role in lymphomagenesis.  (+info)

Concerted evolution of the tandem array encoding primate U2 snRNA (the RNU2 locus) is accompanied by dramatic remodeling of the junctions with flanking chromosomal sequences. (7/466)

The genes encoding primate U2 snRNA are organized as a nearly perfect tandem array (the RNU2 locus) that has been evolving concertedly for >35 Myr since the divergence of baboons and humans. Thus the repeat units of the tandem array are essentially identical within each species, but differ between species. Homogeneity is maintained because any change in one repeat unit is purged from the array or fixed in all other repeats. Intriguingly, the cytological location of RNU2 has remained unchanged despite concerted evolution of the tandem array. We had found previously that junction sequences between the U2 tandem array and flanking DNA were subject to remodeling over a region of 200-300 bp during the past 5 Myr in the hominid lineage. Here we show that the junctions between the U2 tandem array and flanking DNA have undergone dramatic rearrangements over a region of 1 to >10 kbp in the 35 Myr since divergence of the Old World Monkey and hominid lineages. We argue that these rearrangements reflect the high level of genetic activity required to sustain concerted evolution, and propose a model to explain why maintenance of homogeneity within a tandemly repeated multigene family would lead to junctional diversity.  (+info)

Expressed sequence tag (EST) phenotyping of HT-29 cells: cloning of ser/thr protein kinase EMK1, kinesin KIF3B, and of transcripts that include Alu repeated elements. (8/466)

To study the mechanisms that control epithelial commitment and differentiation we have used undifferentiated HT-29 colon cancer cells and a subpopulation of mucus secreting cells obtained by selection of HT-29 cells in 10-6 M methotrexate (M6 cells) as experimental models. We isolated cDNAs encoding transcripts overexpressed in early confluent M6 cells regarding steady-state levels in HT-29 cells by subtractive hybridisation. Fifty-one cDNA clones, corresponding to 34 independent transcripts, were isolated, partially sequenced by their 5' end, and classified into four groups according to their identity: transcripts that included a repeated sequence of the Alu family (10 clones, among them those encoding ribonucleoprotein RNP-L and E-cadherin), transcripts encoded by the mitochondrial genome (nine clones), transcripts encoding components of the protein synthesis machinery (23 clones, including the human ribosomal protein L38 not previously cloned in humans) and nine additional cDNAs that could not be classified in the previous groups. These last included ferritin, cytokeratin 18, translationally controlled human tumour protein (TCHTP), mt-aldehyde dehydrogenase, as well as unknown transcripts (three clones), and the human homologues of the molecular motor kinesin KIF3B and of the ser/thr protein kinase EMK1. Spot dot and Northern blot analyses showed that ser/thr protein kinase EMK1 was differentially expressed in M6 cells when compared with parental HT-29 cells. Steady-state levels of EMK1 were higher in proliferating, preconfluent, M6 and HT-29 cells than in 2 days post confluence (dpc) and 8dpc M6 and HT-29 cells. Transcripts that included an Alu repeat were also shown to be differentially expressed and accumulated in differentiating M6 cells when analysed by Northern blot. The significance of the transcripts cloned is discussed in the context of the commitment and differentiation of the M6 cells to the mucus secreting lineage of epithelial cells.  (+info)

  • Deletion of the Sx Alu repeat in reporter constructs containing hGH-1 3′-flanking sequences increased reporter activity in transfected pituitary GC cells, suggesting this region contained a repressor element. (
  • These results indicate that this cis -acting structural element, downstream of the sequence required for A-to-I catalysis, increases the local concentration of the editing enzyme by attracting ADAR, thus enabling editing in the vicinity. (
  • Adjacent inverted Alu repeats can pair and form long stable stem-loop structures, which are favorable editing substrates, and are also potentially highly abundant in humans (there are 228,607 inverted Alu pairs within 1 kb in genes from the NCBI Reference Sequence (RefSeq) database). (
  • Bisulfite pyrosequencing demonstrates the MIEN1 promoter contains a short interspersed nuclear Alu element (SINE Alu) repeat sequence. (
  • An Sx Alu repeat lies in close proximity to the hGH-1 and hGH-2 genes in the 3′-flanking region. (
  • We show that inverted Alu repeats, expressed in the primate brain, can induce site-selective editing in cis on sites located several hundred nucleotides from the Alu elements. (
  • Analysis of multiple deletion fragments from the 3′-flanking region of the hGH-1 gene revealed a strong orientation- and position-independent silencing activity mapping between nucleotides 2158 and 2572 encompassing the Sx Alu repeat. (
  • Maquat discovered that Alu elements team up with molecules called long noncoding RNAs (lncRNAs) to regulate protein production. (
  • Specifically, long noncoding RNAs and Alu elements recruit the protein Staufen-1 to bind to numerous mRNAs. (
  • Trujillo, MA, Sakagashira, M & Eberhardt, NL 2006, ' The human growth hormone gene contains a silencer embedded within an Alu repeat in the 3′-flanking region ', Molecular Endocrinology , vol. 20, no. 10, pp. 2559-2575. (
  • These results suggest the MIEN1 promoter has a SINE Alu region that is hypermethylated in normal cells leading to repression of the gene. (
  • Furthermore, a computational analysis, based on available RNA-seq data, finds that site-selective editing occurs significantly closer to edited Alu elements than expected. (
  • RNA editing by adenosine to inosine deamination is a widespread phenomenon, particularly frequent in the human transcriptome, largely due to the presence of inverted Alu repeats and their ability to form double-stranded structures - a requisite for ADAR editing. (
  • While scientists have known about the existence of Alu elements for many years, their function, if any, was largely unknown. (
  • Previously, no one knew what Alu elements and long noncoding RNAs did, whether they were junk or if they had any purpose. (
  • id":516028235842,"title":"Round LED Linear Pendant - Model Alu Round 38 [Profile Only]","handle":"round-led-linear-pendant-model-ro38-profile-only","description":"\u003cp\u003eIt is a high quality, rigid and a very solid round profile made of anodized aluminum designed to be used with LED light sources. (
  • Refined mapping revealed that the silencer was a complex element comprising four discrete entities, including a core repressor domain (CRD), an antisilencer domain (ASE) that contains elements mediating the orientation-independent silencer activity, and two domains flanking the CRD/ASE that modulate silencer activity in a CRD-dependent manner. (
  • The human (h) GH locus contains 44 complete and four partial Alu elements. (
  • Maquat and the study's first author, Chenguang Gong, a graduate student in the Department of Biochemistry and Biophysics at the Medical Center, found that long noncoding RNAs and Alu elements work together to trigger a process known as SMD (Staufen 1-mediated mRNA decay). (
  • Although this editing inducer element (IE) is hyper-edited, mutational analysis shows that it is the double-stranded structure rather than editing that is important for the distal editing induction. (
  • Mutagenic NHEJ repair involving divergent Alu elements may represent a common repair event in primate genomes. (
  • Alu elements of different kinds occur in large numbers in primate genomes. (
  • Alu elements are major contributors to lineage-specific new exons in primate and human genomes. (
  • 2010. Endogenous non-retroviral RNA virus elements in mammalian genomes. (
  • Mammalian transposable elements have been restructuring their host genomes for millions of years, to both deleterious and advantageous effects. (
  • Transposable elements (TEs) represent a variable but often sizeable fraction of genomes (e.g. (
  • Evolutionists have generally assumed that Alu elements arose through being copied and spliced throughout various animals' genomes. (
  • Mobile, or transposable, elements are prevalent in the genomes of all plants and animals. (
  • This study highlights the importance of noncoding RNA and transposable elements in the regulation of gene expression and in the evolution of gene expression networks in mammalian genomes," said coauthor Manuel Ares, professor of molecular, cell, and developmental biology at UC Santa Cruz. (
  • How natural selection acts to limit the proliferation of transposable elements (TEs) in genomes has been of interest to evolutionary biologists for many years. (
  • DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration ,' Nature 17 March 2011) now points to one likely cause of AMD, and in the process provides a chilling example of what can happen when the parasitic Alu elements in our genomes (see the previous post for an introduction) are left unrestrained. (
  • There is, in fact, some scientific disagreement about functions of various elements in genomes, but it's not the crude standoff that ID apologists depict, and it has very little to do with 'Darwinism. (
  • Alternative splicing of Alu exons--two arms are better than one. (
  • Recent studies indicate that some Alu exons have high transcript inclusion levels or tissue-specific splicing profiles, and may play important regulatory roles in modulating mRNA degradation or translational efficiency. (
  • However, the contribution of Alu exons to the human proteome remains unclear and controversial. (
  • The prevailing view is that exons derived from young repetitive elements, such as Alu elements, are restricted to regulatory functions and have not had adequate evolutionary time to be incorporated into stable, functional proteins. (
  • We adopt a proteotranscriptomics approach to systematically assess the contribution of Alu exons to the human proteome. (
  • Using RNA sequencing, ribosome profiling, and proteomics data from human tissues and cell lines, we provide evidence for the translational activities of Alu exons and the presence of Alu exon derived peptides in human proteins. (
  • Together, these data have established the regulatory roles of Alu exons in multiple aspects of RNA metabolism including translation and degradation. (
  • They identified numerous instances of 'in-frame' Alu exons in the coding region of human mRNAs that are predicted to add Alu -derived peptides to the protein products. (
  • Here, we assess the interplay of splicing repression by hnRNPC and nonsense-mediated mRNA decay (NMD) in the quality control and evolution of new Alu-exons. (
  • Once the 3' splice site at ancient Alu-exons reaches a stable phase, splicing repression by hnRNPC decreases, but the exons generally remain sensitive to NMD. (
  • Thus, it is important to understand the protective molecular mechanisms imposing constraints on the emergence and expression of Alu-exons. (
  • Thus, the U-tract:hnRNPC interaction is crucial to prevent the splicing machinery from accessing cryptic splice sites at Alu-exons. (
  • Comparative meta-analysis with the 80 other CNV cases from 12 publications describing STK11 mutations in patients with PJS revealed the participation of specific Alu elements in all deletions of exons 2-3 so far described. (
  • a) Alu exonization: a hypothetical gene constituted of three exons (light grey, white and dark grey boxes) is shown with its splicing pattern (dashed lines above gene). (
  • Alu elements do not encode for protein products. (
  • In the case of the RNA editing enzyme ADARB1, which contains an Alu exon peptide in its catalytic domain, RNA sequencing analyses of A-to-I editing demonstrate that both the Alu exon skipping and inclusion isoforms encode active enzymes. (
  • Several Alu subfamilies are known to be actively transposing and it is thought that a new insertion occurs approximately every 20 births in humans ( Cordaux & Batzer, 2009 ). (
  • Alu RNA is increased in the RPE of humans with GA, and this pathogenic RNA induces human RPE cytotoxicity and RPE degeneration in mice. (
  • Shown is Alu an active SINE in humans. (
  • These elements are not present in humans, and essentially all are defective, so the source of their RT in trans remains unknown. (
  • RPE cells from mouse or humans were transfected with in vitro transcribed Alu RNA or a plasmid encoding an Alu element. (
  • Here, we report that human mRNAs containing inverted Alu elements are present in the mammalian cytoplasm. (
  • Thus, we have defined unexpected roles for Alu elements, lncRNAs and mRNAs. (
  • In other studies, we have found that STAU1 (and probably STAU2) binding to 3'UTR inverted Alu elements competes with binding of the largely nuclear paraspeckle protein p54nrb and largely cytoplasmic protein kinase R (PKR) to mediate, respectively, the nuclear export and cytoplasmic translation of a number of mRNAs that contain these elements. (
  • However, the maintenance and methylation status of each CpG site within Alu elements ( Alu ) and its methylation status have not well characterized. (
  • A high correlation coefficient of methylation was observed between Alu clones and CpG site J (0.963), A (0.950), H (0.946), D (0.945). (
  • The most common target site coincides with the evolutionary most conserved part of Alu. (
  • Thus, a dual relationship exists between an evolutionary young miRNA cluster and their Alu targets that may have evolved in the same time window. (
  • Because many of the Alu elements within C19MC are evolutionary old (AluJ and AluS), expansion of the cluster may have occurred at an early wave of expansion of the Alu elements. (
  • The target sites are relatively unspecific so that the chance of an independent integration of exactly the same element into one specific site in different taxa is not large and may even be negligible over evolutionary time scales. (
  • The so-called 'junk' DNAs that have perplexed creationists and evolutionary scientists alike may be the very elements that can explain the mechanisms by which God is at work in His creation now and in the past. (
  • In 1988, Jerzy Jurka and Temple Smith discovered that Alu elements were split in two major subfamilies known as AluJ (named after Jurka) and AluS (named after Smith), and other Alu subfamilies were also independently discovered by several groups. (
  • Altering Genomic Integrity: Heavy Metal Exposure Promotes Transposable Element-Mediated Damage. (
  • Here, I describe the evolution of Alu elements in lncRNA and mRNA. (
  • We showed for the first time a tissue-specific decrease in the pre-mRNA content of the gene allele bearing L1 or Alu inserts relative to the other allele of the same gene lacking the retroelement. (
  • A cis-acting element in the 3'-untranslated region of human TNF-alpha mRNA renders splicing dependent on the activation of protein kinase PKR. (
  • citation needed]This is because insertion of an Alu element occurs only 100 - 200 times per million years, and no known mechanism of deletion of one has been found. (
  • Here we present a novel 7001 bps deletion of STK11 gene fragment, in which we identified the presence of breakpoints (BPs) within the Alu elements. (
  • Mutations may also result from insertion or deletion of segments of DNA due to mobile genetic elements . (
  • Analysis of multiple deletion fragments from the 3′-flanking region of the hGH-1 gene revealed a strong orientation- and position-independent silencing activity mapping between nucleotides 2158 and 2572 encompassing the Sx Alu repeat. (
  • We use a new reporter assay to show that repair of DSBs results in Alu-mediated deletions that resolve through several distinct repair pathways. (
  • A number of different pathways can give rise to these Alu/Alu deletions, including single-strand annealing (SSA) repair that may predominate when there are high levels of homology, and mechanisms such as microhomology-mediated end joining (MMEJ) where the microhomology happens to be 'in register' between the two Alu elements, allowing formation of a single chimeric Alu element [ 7 ]. (
  • In genetics, presence or lack thereof of a recently inserted Alu element may be a good property to consider when studying human evolution. (
  • Alu elements in ANRIL non-coding RNA at chromosome 9p21 modulate atherogenic cell functions through trans -regulation of gene networks," PLoS Genetics , vol. 9, no. 7, Article ID e1003588, 2013. (
  • It is suggested that Alu elements have played potentially important roles in genotypic and phenotypic evolution in the hominid lineage. (
  • The formation of noncanonical structures in Alu bcl2 dsDNA and their absence in the case of Alu-PQS have been shown using DMS-footprinting and atomic force microscopy (AFM). (
  • The size of the amplification product(s) will depend upon the presence or absence of the Alu insertion at the TPA-25 locus on each copy of chromosome 8. (