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Pesquisa : G02.111.570.080.708.330.800.800 [Categoria DeCS]
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[PMID]:29190290
[Au] Autor:Rooney MF; Porter RK; Katz LM; Hill EW
[Ad] Endereço:UCD School of Agriculture and Food Science, University College Dublin, Belfield, Dublin 4, Ireland.
[Ti] Título:Skeletal muscle mitochondrial bioenergetics and associations with myostatin genotypes in the Thoroughbred horse.
[So] Source:PLoS One;12(11):e0186247, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Variation in the myostatin (MSTN) gene has been reported to be associated with race distance, body composition and skeletal muscle fibre composition in the horse. The aim of the present study was to test the hypothesis that MSTN variation influences mitochondrial phenotypes in equine skeletal muscle. Mitochondrial abundance and skeletal muscle fibre types were measured in whole muscle biopsies from the gluteus medius of n = 82 untrained (21 ± 3 months) Thoroughbred horses. Skeletal muscle fibre type proportions were significantly (p < 0.01) different among the three MSTN genotypes and mitochondrial content was significantly (p < 0.01) lower in the combined presence of the C-allele of SNP g.66493737C>T (C) and the SINE insertion 227 bp polymorphism (I). Evaluation of mitochondrial complex activities indicated higher combined mitochondrial complex I+III and II+III activities in the presence of the C-allele / I allele (p ≤ 0.05). The restoration of complex I+III and complex II+III activities following addition of exogenous coenzyme Q1 (ubiquinone1) (CoQ1) in vitro in the TT/NN (homozygous T allele/homozygous no insertion) cohort indicated decreased coenzyme Q in these animals. In addition, decreased gene expression in two coenzyme Q (CoQ) biosynthesis pathway genes (COQ4, p ≤ 0.05; ADCK3, p ≤ 0.01) in the TT/NN horses was observed. This study has identified several mitochondrial phenotypes associated with MSTN genotype in untrained Thoroughbred horses and in addition, our findings suggest that nutritional supplementation with CoQ may aid to restore coenzyme Q activity in TT/NN horses.
[Mh] Termos MeSH primário: Metabolismo Energético
Genótipo
Cavalos/metabolismo
Mitocôndrias Musculares/metabolismo
Músculo Esquelético/metabolismo
Miostatina/genética
[Mh] Termos MeSH secundário: Fatores Etários
Animais
Feminino
Cavalos/genética
Masculino
Fenótipo
Condicionamento Físico Animal
Polimorfismo de Nucleotídeo Único
Elementos Nucleotídeos Curtos e Dispersos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Myostatin)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171226
[Lr] Data última revisão:
171226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171201
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0186247


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[PMID]:28957425
[Au] Autor:Smith CEL; Alexandraki A; Cordery SF; Parmar R; Bonthron DT; Valleley EMA
[Ad] Endereço:School of Medicine, University of Leeds, St. James's University Hospital, Leeds, United Kingdom.
[Ti] Título:A tissue-specific promoter derived from a SINE retrotransposon drives biallelic expression of PLAGL1 in human lymphocytes.
[So] Source:PLoS One;12(9):e0185678, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The imprinted gene PLAGL1 is an important regulator of apoptosis and cell cycle arrest. Loss of its expression has been implicated in tumorigenesis in a range of different cancers, and overexpression during fetal development causes transient neonatal diabetes mellitus (TNDM). PLAGL1 lies within an imprinted region of chromosome 6q24, and monoallelic expression from the major, differentially methylated promoter (P1) occurs in most human tissues. However, in peripheral blood leukocytes, the active promoter (P2) is non-imprinted and drives biallelic transcription. We report here a novel PLAGL1 promoter (P5) derived from the insertion of a primate-specific, MIR3 SINE retrotransposon. P5 is highly utilized in lymphocytes, particularly in T cells, and like P2, directs biallelic transcription. Our results show that it is important to consider P5 in relation to PLAGL1 function in T cells when investigating the dysregulation of this gene.
[Mh] Termos MeSH primário: Alelos
Proteínas de Ciclo Celular/genética
Regiões Promotoras Genéticas
Retroelementos
Elementos Nucleotídeos Curtos e Dispersos/genética
Fatores de Transcrição/genética
Proteínas Supressoras de Tumor/genética
[Mh] Termos MeSH secundário: Linfócitos B/metabolismo
Ilhas de CpG
Seres Humanos
RNA Mensageiro/genética
Reação em Cadeia da Polimerase em Tempo Real
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Linfócitos T/metabolismo
Transcrição Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cell Cycle Proteins); 0 (PLAGL1 protein, human); 0 (RNA, Messenger); 0 (Retroelements); 0 (Transcription Factors); 0 (Tumor Suppressor Proteins)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170929
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0185678


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[PMID]:28704426
[Au] Autor:Azizi H; Romão TP; Santos Charret K; Padmanabhan PK; de Melo Neto OP; Müller-McNicoll M; Papadopoulou B
[Ad] Endereço:Research Center in Infectious Diseases, CHU de Quebec Research Center-University Laval, Quebec, QC. Canada.
[Ti] Título:RNA secondary structure and nucleotide composition of the conserved hallmark sequence of Leishmania SIDER2 retroposons are essential for endonucleolytic cleavage and mRNA degradation.
[So] Source:PLoS One;12(7):e0180678, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We have reported previously that Short Interspersed Degenerate Retroposons of the SIDER2 subfamily, largely located within 3'UTRs of Leishmania transcripts, promote rapid turnover of mRNAs through endonucleolytic cleavage within the highly conserved second tandem 79-nt hallmark sequence (79-nt SII). Here, we used site-directed mutagenesis and in silico RNA structural studies to delineate the cis-acting requirements within 79-nt SII for cleavage and mRNA degradation. The putative cleavage site(s) and other nucleotides predicted to alter the RNA secondary structure of 79-nt SII were either deleted or mutated and their effect on mRNA turnover was monitored using a gene reporter system. We found that short deletions of 8-nt spanning the two predicted cleavage sites block degradation of SIDER2-containing transcripts, leading to mRNA accumulation. Furthermore, single or double substitutions of the dinucleotides targeted for cleavage as well as mutations altering the predicted RNA secondary structure encompassing both cleavage sites also prevent mRNA degradation, confirming that these dinucleotides are the bona fide cleavage sites. In line with these results, we show that stage-regulated SIDER2 inactivation correlates with the absence of endonucleolytic cleavage. Overall, these data demonstrate that both cleavage sites within the conserved 79-nt SII as well as RNA folding in this region are essential for SIDER2-mediated mRNA decay, and further support that SIDER2-harboring transcripts are targeted for degradation by endonucleolytic cleavage.
[Mh] Termos MeSH primário: Leishmania/genética
RNA Mensageiro/química
RNA de Protozoário/química
Elementos Nucleotídeos Curtos e Dispersos
[Mh] Termos MeSH secundário: Sequência de Bases
Simulação por Computador
Sequência Conservada
Modelos Moleculares
Mutagênese Sítio-Dirigida
Conformação de Ácido Nucleico
Estabilidade de RNA
Deleção de Sequência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Messenger); 0 (RNA, Protozoan)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170714
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0180678


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[PMID]:28658256
[Au] Autor:Nakajima R; Sato T; Ogawa T; Okano H; Noce T
[Ad] Endereço:Department of Physiology, Keio University School of Medicine, 35 Shinamomachi, Shinjuku-ku, Tokyo, Japan.
[Ti] Título:A noncoding RNA containing a SINE-B1 motif associates with meiotic metaphase chromatin and has an indispensable function during spermatogenesis.
[So] Source:PLoS One;12(6):e0179585, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A search for early response genes that are activated following germ cell induction from mouse embryonic stem cells in vitro led us to the isolation of a long noncoding RNA that contains a SINE (short interspersed element)-B1F motif that was named R53. In situ hybridization and northern blot analyses revealed that the R53 subfragment RNA bears a B1F motif, is processed from the primary transcript, is expressed in adult testis and is predominantly localized in meiotic metaphase chromatin during spermatogenesis. Recent studies of chromosome-associated RNAs have explored novel functions of noncoding RNAs. Specifically, chromosome-bound noncoding RNAs function not only as structural components of chromosome but also as scaffolds that recruit epigenetic modulators for transcriptional regulation, and they are dynamically rearranged during the cell cycle. However, few studies have explored meiotic chromatin; thus, R53 RNA appears to be the first long noncoding RNA to be tightly associated with the metaphase chromatin during spermatogenesis. Furthermore, R53 knockdown using a lentivirus-mediated RNAi injected into mouse testis and organ culture of the fragments revealed a remarkable reduction in postmeiotic cells and irregular up-regulation of several postmeiotic genes, which suggests the possibility that the SINE-B1-derived noncoding RNA R53 plays an indispensable role in the transcriptional regulation of key spermatogenesis genes.
[Mh] Termos MeSH primário: Cromatina/metabolismo
Metáfase/fisiologia
RNA não Traduzido/metabolismo
Elementos Nucleotídeos Curtos e Dispersos/genética
Espermatogênese/fisiologia
[Mh] Termos MeSH secundário: Animais
Regulação da Expressão Gênica
Masculino
Camundongos
Interferência de RNA
RNA não Traduzido/genética
Testículo/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chromatin); 0 (RNA, Untranslated)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170920
[Lr] Data última revisão:
170920
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170629
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0179585


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[PMID]:28642606
[Au] Autor:Burns KH
[Ad] Endereço:Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
[Ti] Título:Transposable elements in cancer.
[So] Source:Nat Rev Cancer;17(7):415-424, 2017 Jul.
[Is] ISSN:1474-1768
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Transposable elements give rise to interspersed repeats, sequences that comprise most of our genomes. These mobile DNAs have been historically underappreciated - both because they have been presumed to be unimportant, and because their high copy number and variability pose unique technical challenges. Neither impediment now seems steadfast. Interest in the human mobilome has never been greater, and methods enabling its study are maturing at a fast pace. This Review describes the activity of transposable elements in human cancers, particularly long interspersed element-1 (LINE-1). LINE-1 sequences are self-propagating, protein-coding retrotransposons, and their activity results in somatically acquired insertions in cancer genomes. Altered expression of transposable elements and animation of genomic LINE-1 sequences appear to be hallmarks of cancer, and can be responsible for driving mutations in tumorigenesis.
[Mh] Termos MeSH primário: Transformação Celular Neoplásica/genética
Elementos de DNA Transponíveis
Elementos Nucleotídeos Longos e Dispersos/genética
Neoplasias/genética
Fases de Leitura Aberta/genética
[Mh] Termos MeSH secundário: Seres Humanos
Repetições Minissatélites/genética
Regiões Promotoras Genéticas/genética
RNA/genética
Elementos Nucleotídeos Curtos e Dispersos/genética
Sequências Repetidas Terminais/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (DNA Transposable Elements); 63231-63-0 (RNA)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170823
[Lr] Data última revisão:
170823
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170624
[St] Status:MEDLINE
[do] DOI:10.1038/nrc.2017.35


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[PMID]:28505260
[Au] Autor:Luchetti A; Plazzi F; Mantovani B
[Ad] Endereço:Dipartimento di Scienze Biologiche, Geologiche e Ambientali - Università di Bologna, Italy.
[Ti] Título:Evolution of Two Short Interspersed Elements in Callorhinchus milii (Chondrichthyes, Holocephali) and Related Elements in Sharks and the Coelacanth.
[So] Source:Genome Biol Evol;9(6), 2017 Jun 01.
[Is] ISSN:1759-6653
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Short interspersed elements (SINEs) are non-autonomous retrotransposons. Although they usually show fast evolutionary rates, in some instances highly conserved domains (HCDs) have been observed in elements with otherwise divergent sequences and from distantly related species. Here, we document the life history of two HCD-SINE families in the elephant shark Callorhinchus milii, one specific to the holocephalan lineage (CmiSINEs) and another one (SacSINE1-CM) with homologous elements in sharks and the coelacanth (SacSINE1s, LmeSINE1s). The analyses of their relationships indicated that these elements share the same 3'-tail, which would have allowed both elements to rise to high copy number by exploiting the C. milii L2-2_CM long interspersed element (LINE) enzymes. Molecular clock analysis on SINE activity in C. milii genome evidenced two replication bursts occurring right after two major events in the holocephalan evolution: the end-Permian mass extinction and the radiation of modern Holocephali. Accordingly, the same analysis on the coelacanth homologous elements, LmeSINE1, identified a replication wave close to the split age of the two extant Latimeria species. The genomic distribution of the studied SINEs pointed out contrasting results: some elements were preferentially sorted out from gene regions, but accumulated in flanking regions, while others appear more conserved within genes. Moreover, data from the C. milii transcriptome suggest that these SINEs could be involved in miRNA biogenesis and may be targets for miRNA-based regulation.
[Mh] Termos MeSH primário: Elementos de DNA Transponíveis
Evolução Molecular
Peixes/genética
Tubarões/genética
Elementos Nucleotídeos Curtos e Dispersos
[Mh] Termos MeSH secundário: Animais
Sequência de Bases
Sequência Conservada
Elementos Nucleotídeos Longos e Dispersos
Análise de Sequência de DNA/métodos
Transcriptoma
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA Transposable Elements)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170516
[St] Status:MEDLINE
[do] DOI:10.1093/gbe/evx094


  7 / 519 MEDLINE  
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[PMID]:28334904
[Au] Autor:Karijolich J; Zhao Y; Alla R; Glaunsinger B
[Ad] Endereço:Howard Hughes Medical Institute, University of California, Berkeley, CA 94720-3370, USA.
[Ti] Título:Genome-wide mapping of infection-induced SINE RNAs reveals a role in selective mRNA export.
[So] Source:Nucleic Acids Res;45(10):6194-6208, 2017 Jun 02.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Short interspersed nuclear elements (SINEs) are retrotransposons evolutionarily derived from endogenous RNA Polymerase III RNAs. Though SINE elements have undergone exaptation into gene regulatory elements, how transcribed SINE RNA impacts transcriptional and post-transcriptional regulation is largely unknown. This is partly due to a lack of information regarding which of the loci have transcriptional potential. Here, we present an approach (short interspersed nuclear element sequencing, SINE-seq), which selectively profiles RNA Polymerase III-derived SINE RNA, thereby identifying transcriptionally active SINE loci. Applying SINE-seq to monitor murine B2 SINE expression during a gammaherpesvirus infection revealed transcription from 28 270 SINE loci, with ∼50% of active SINE elements residing within annotated RNA Polymerase II loci. Furthermore, B2 RNA can form intermolecular RNA-RNA interactions with complementary mRNAs, leading to nuclear retention of the targeted mRNA via a mechanism involving p54nrb. These findings illuminate a pathway for the selective regulation of mRNA export during stress via retrotransposon activation.
[Mh] Termos MeSH primário: Regulação da Expressão Gênica/genética
RNA Mensageiro/genética
Elementos Nucleotídeos Curtos e Dispersos/genética
[Mh] Termos MeSH secundário: Animais
Transporte Biológico/genética
Proteínas de Ciclo Celular/genética
Técnicas de Silenciamento de Genes
Infecções por Herpesviridae/genética
Camundongos
Células NIH 3T3
Proteínas Associadas à Matriz Nuclear/metabolismo
Interferência de RNA
RNA Polimerase III/genética
RNA Mensageiro/metabolismo
Proteínas de Ligação a RNA/metabolismo
Retroelementos/fisiologia
Rhadinovirus
Análise de Sequência de DNA
Estresse Fisiológico/genética
Frações Subcelulares/metabolismo
Transcrição Genética
Infecções Tumorais por Vírus/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cell Cycle Proteins); 0 (Nuclear Matrix-Associated Proteins); 0 (RNA, Messenger); 0 (RNA-Binding Proteins); 0 (Retroelements); 0 (SGOL2 protein, mouse); 0 (p54nrb protein, mouse); EC 2.7.7.6 (RNA Polymerase III)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170324
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx180


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[PMID]:28131659
[Au] Autor:Sharma S; Banyal N; Singh M; Mandal AK; Bhattacharya S; Paul J
[Ad] Endereço:School of Environmental Sciences, Jawaharlal Nehru University, New Delhi, India.
[Ti] Título:SINE polymorphism reveals distinct strains of Entamoeba histolytica from North India.
[So] Source:Exp Parasitol;175:28-35, 2017 Apr.
[Is] ISSN:1090-2449
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Entamoeba histolytica is an intestinal parasite causing significant morbidity and mortality in the developing world. More tools are needed to understand the epidemiology and molecular pathogenesis of amebiasis. Virulence pattern of E. histolytica could be linked with the genotype of a strain. Several loci showing insertion polymorphism of retrotransposable short interspersed nuclear elements EhSINE1 and EhSINE2 have been reported among laboratory strains of E. histolytica. The present study was undertaken to validate this observation in clinical isolates from north India. Our results indicate that the Indian samples show a different propensity of SINE retention or loss at two of the polymorphic loci compared with non-Indian samples. Statistical analysis of different loci revealed Locus 17 of EhSINE1as a potential geographical marker for distinguishing Indian isolates from non Indian isolates.
[Mh] Termos MeSH primário: DNA de Protozoário/química
Entamoeba histolytica/classificação
Entamebíase/parasitologia
Polimorfismo Genético
Elementos Nucleotídeos Curtos e Dispersos/genética
[Mh] Termos MeSH secundário: Southern Blotting
Elementos de DNA Transponíveis
DNA de Protozoário/isolamento & purificação
Entamoeba histolytica/genética
Entamoeba histolytica/patogenicidade
Entamebíase/epidemiologia
Fezes/parasitologia
Genótipo
Seres Humanos
Immunoblotting
Índia/epidemiologia
Reação em Cadeia da Polimerase
Virulência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA Transposable Elements); 0 (DNA, Protozoan)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170328
[Lr] Data última revisão:
170328
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170130
[St] Status:MEDLINE


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[PMID]:27714457
[Au] Autor:Barghini E; Mascagni F; Natali L; Giordani T; Cavallini A
[Ad] Endereço:Department of Agriculture, Food and Environment, University of Pisa, Via del Borghetto 80, I-56124, Pisa, Italy.
[Ti] Título:Identification and characterisation of Short Interspersed Nuclear Elements in the olive tree (Olea europaea L.) genome.
[So] Source:Mol Genet Genomics;292(1):53-61, 2017 Feb.
[Is] ISSN:1617-4623
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Short Interspersed Nuclear Elements (SINEs) are nonautonomous retrotransposons in the genome of most eukaryotic species. While SINEs have been intensively investigated in humans and other animal systems, SINE identification has been carried out only in a limited number of plant species. This lack of information is apparent especially in non-model plants whose genome has not been sequenced yet. The aim of this work was to produce a specific bioinformatics pipeline for analysing second generation sequence reads of a non-model species and identifying SINEs. We have identified, for the first time, 227 putative SINEs of the olive tree (Olea europaea), that constitute one of the few sets of such sequences in dicotyledonous species. The identified SINEs ranged from 140 to 362 bp in length and were characterised with regard to the occurrence of the tRNA domain in their sequence. The majority of identified elements resulted in single copy or very lowly repeated, often in association with genic sequences. Analysis of sequence similarity allowed us to identify two major groups of SINEs showing different abundances in the olive tree genome, the former with sequence similarity to SINEs of Scrophulariaceae and Solanaceae and the latter to SINEs of Salicaceae. A comparison of sequence conservation between olive SINEs and LTR retrotransposon families suggested that SINE expansion in the genome occurred especially in very ancient times, before LTR retrotransposon expansion, and presumably before the separation of the rosids (to which Oleaceae belong) from the Asterids. Besides providing data on olive SINEs, our results demonstrate the suitability of the pipeline employed for SINE identification. Applying this pipeline will favour further structural and functional analyses on these relatively unknown elements to be performed also in other plant species, even in the absence of a reference genome, and will allow establishing general evolutionary patterns for this kind of repeats in plants.
[Mh] Termos MeSH primário: Olea/genética
Elementos Nucleotídeos Curtos e Dispersos
[Mh] Termos MeSH secundário: Biologia Computacional
DNA de Plantas/genética
Filogenia
Análise de Sequência de DNA
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Plant)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:171007
[Lr] Data última revisão:
171007
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161008
[St] Status:MEDLINE
[do] DOI:10.1007/s00438-016-1255-3


  10 / 519 MEDLINE  
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[PMID]:27782844
[Au] Autor:Tajaddod M; Tanzer A; Licht K; Wolfinger MT; Badelt S; Huber F; Pusch O; Schopoff S; Janisiw M; Hofacker I; Jantsch MF
[Ad] Endereço:Department of Chromosome Biology, Max F. Perutz Laboratories, University of Vienna, Dr. Bohr Gasse 9/5, Vienna, A-1030, Austria.
[Ti] Título:Transcriptome-wide effects of inverted SINEs on gene expression and their impact on RNA polymerase II activity.
[So] Source:Genome Biol;17(1):220, 2016 Oct 25.
[Is] ISSN:1474-760X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Short interspersed elements (SINEs) represent the most abundant group of non-long-terminal repeat transposable elements in mammalian genomes. In primates, Alu elements are the most prominent and homogenous representatives of SINEs. Due to their frequent insertion within or close to coding regions, SINEs have been suggested to play a crucial role during genome evolution. Moreover, Alu elements within mRNAs have also been reported to control gene expression at different levels. RESULTS: Here, we undertake a genome-wide analysis of insertion patterns of human Alus within transcribed portions of the genome. Multiple, nearby insertions of SINEs within one transcript are more abundant in tandem orientation than in inverted orientation. Indeed, analysis of transcriptome-wide expression levels of 15 ENCODE cell lines suggests a cis-repressive effect of inverted Alu elements on gene expression. Using reporter assays, we show that the negative effect of inverted SINEs on gene expression is independent of known sensors of double-stranded RNAs. Instead, transcriptional elongation seems impaired, leading to reduced mRNA levels. CONCLUSIONS: Our study suggests that there is a bias against multiple SINE insertions that can promote intramolecular base pairing within a transcript. Moreover, at a genome-wide level, mRNAs harboring inverted SINEs are less expressed than mRNAs harboring single or tandemly arranged SINEs. Finally, we demonstrate a novel mechanism by which inverted SINEs can impact on gene expression by interfering with RNA polymerase II.
[Mh] Termos MeSH primário: RNA Polimerase II/genética
Elementos Nucleotídeos Curtos e Dispersos/genética
Transcrição Genética
Transcriptoma/genética
[Mh] Termos MeSH secundário: Elementos Alu/genética
Linhagem Celular
Evolução Molecular
Regulação da Expressão Gênica
Genoma Humano
Seres Humanos
RNA de Cadeia Dupla/genética
RNA Mensageiro/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Double-Stranded); 0 (RNA, Messenger); EC 2.7.7.- (RNA Polymerase II)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170614
[Lr] Data última revisão:
170614
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161027
[St] Status:MEDLINE



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