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MICRORNA研究经典文献MicroRNAs (miRNAs)是一种大小约2123个碱基的单链小分子RNA,是由具有发夹结构的约70-90个碱基大小的单链RNA前体经过dicer酶加工后生成,不同于siRNA(双链)但是和siRNA密切相关。据推测,这些非编码小分子RNA(miRNAs)参与调控基因表达,但其机制区别于siRNA介导的mRNA降解。第一个被确认的miRNA是在线虫中首次发现的lin-4 和let-7,随后多个研究小组在包括人类、果蝇、植物等多种生物物种中鉴别出数百个miRNAs。最早被发现的两个miRNAslin-4 and let-7被认为是通过不完全互补结合到目标靶mRNA 3非编码区端,以一种未知方式诱发蛋白质翻译抑制,进而抑制蛋白质合成,阻断mRNA的翻译。多个果蝇miRNAs也被发现和他们的目标靶mRNAs的3非编码区有部分同源。由于miRNAs和其潜在的目标靶之间并非完全互补,这使得通过信息学的方法鉴定miRNA的目标靶位点变得困难。因而也无法确定miRNAs的作用方式是什么,以何种机制影响mRNA的翻译,以何种方式调控基因表达。miRNAs的作用目标靶和活性机制一直是各地的研究人员的关注热点。 收集了一些microrna研究最重要的文献,供大家参考Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes aremicroRNAtargets作者:Lewis, BP; Burge, CB; Bartel, DPCELL卷:120期:1页:15-20出版年:JAN 14 2005出版商处的全文关闭摘要We predict regulatory targets of vertebrate microRNAs (miRNAs) by identifying mRNAs with conserved complementarity to the seed (nucleotides 2-7) of the miRNA. An overrepresentation of conserved adenosines flanking the seed complementary sites in mRNAs indicates that primary sequence determinants can supplement base pairing to specify miRNA target recognition. In a four-genome analysis of 3 UTRs, approximately 13,000 regulatory relationships were detected above the estimate of false-positive predictions, thereby implicating as miRNA targets more than 5300 human genes, which represented 30% of our gene set. Targeting was also detected in open reading frames. In sum, well over one third of human genes appear to be conserved miRNA targets.被引频次:4,546(来自所有数据库)MicroRNAexpression profiles classify human cancers作者:Lu, J; Getz, G; Miska, EA; 等.NATURE卷:435期:7043页:834-838出版年:JUN 9 2005关闭摘要Recent work has revealed the existence of a class of small non-coding RNA species, known as microRNAs ( miRNAs), which have critical functions across various biological processes(1,2). Here we use a new, bead-based flow cytometric miRNA expression profiling method to present a systematic expression analysis of 217 mammalian miRNAs from 334 samples, including multiple human cancers. The miRNA profiles are surprisingly informative, reflecting the developmental lineage and differentiation state of the tumours. We observe a general downregulation of miRNAs in tumours compared with normal tissues. Furthermore, we were able to successfully classify poorly differentiated tumours using miRNA expression profiles, whereas messenger RNA profiles were highly inaccurate when applied to the same samples. These findings highlight the potential of miRNA profiling in cancer diagnosis.被引频次:3,853(来自所有数据库)The functions of animal microRNAs作者:Ambros, VNATURE卷:431期:7006页:350-355出版年:SEP 16 2004被引频次:3,273(来自所有数据库)Oncomirs - microRNAs with a role in cancer作者:Esquela-Kerscher, A; Slack, FJNATURE REVIEWS CANCER卷:6期:4页:259-269出版年:APR 2006关闭摘要MicroRNAs (miRNAs) are an abundant class of small non-protein-coding RNAs that function as negative gene regulators. They regulate diverse biological processes, and bioinformatic data indicates that each miRNA can control hundreds of gene targets, underscoring the potential influence of miRNAs on almost every genetic pathway. Recent evidence has shown that miRNA mutations or mis-expression correlate with various human cancers and indicates that miRNAs can function as tumour suppressors and oncogenes. miRNAs have been shown to repress the expression of important cancer-related genes and might prove useful in the diagnosis and treatment of cancer.被引频次:2,617(来自所有数据库)AmicroRNAexpression signature of human solid tumors defines cancer gene targets作者:Volinia, S; Calin, GA; Liu, CG; 等.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA卷:103期:7页:2257-2261出版年:FEB 14 2006关闭摘要Small noncoding microRNAs (miRNAs) can contribute to cancer development and progression and are differentially expressed in normal tissues and cancers. From a large-scale miRnome analysis on 540 samples including lung, breast, stomach, prostate, colon, and pancreatic tumors, we identified a solid cancer miRNA signature composed by a large portion of overexpressed miRNAs. Among these miRNAs are some with well characterized cancer association, such as miR-17-5p, miR-20a, miR-21, miR-92, miR-106a, and miR-155. The predicted targets for the differentially expressed miRNAs are significantly enriched for protein-coding tumor suppressors and oncogenes (P 90% of uniquely mapped reads fell within known exons, the remaining data suggest new and revised gene models, including changed or additional promoters, exons and 3 untranscribed regions, as well as new candidate microRNA precursors. RNA splice events, which are not readily measured by standard gene expression microarray or serial analysis of gene expression methods, were detected directly by mapping splice-crossing sequence reads. We observed 1.45 x 10(5) distinct splices, and alternative splices were prominent, with 3,500 different genes expressing one or more alternate internal splices.被引频次:2,450(来自所有数据库)MicroRNAsignatures in human cancers作者:Calin, George A.; Croce, Carlo M.NATURE REVIEWS CANCER卷:6期:11页:857-866出版年:NOV 2006关闭摘要MicroRNA (miRNA) alterations are involved in the initiation and progression of human cancer. The causes of the widespread differential expression of miRNA genes in malignant compared with normal cells can be explained by the location of these genes in cancer-associated genomic regions, by epigenetic mechanisms and by alterations in the miRNA processing machinery. MiRNA-expression profiling of human tumours has identified signatures associated with diagnosis, staging, progression, prognosis and response to treatment. In addition, profiling has been exploited to identify miRNA genes that might represent downstream targets of activated oncogenic pathways, or that target protein-coding genes involved in cancer.被引频次:2,356Prediction of mammalianmicroRNAtargets作者:Lewis, BP; Shih, IH; Jones-Rhoades, MW; 等.CELL卷:115期:7页:787-798出版年:DEC 26 2003出版商处的全文关闭摘要MicroRNAs (miRNAs) can play important gene regulatory roles in nematodes, insects, and plants by base-pairing to mRNAs to specify posttranscriptional repression of these messages. However, the mRNAs regulated by vertebrate miRNAs are all unknown. Here we predict more than 400 regulatory target genes for the conserved vertebrate miRNAs by identifying mRNAs with conserved pairing to the 5 region of the miRNA and evaluating the number and quality of these complementary sites. Rigorous tests using shuffled miRNA controls supported a majority of these predictions, with the fraction of false positives estimated at 31% for targets identified in human, mouse, and rat and 22% for targets identified in pufferfish as well as mammals. Eleven predicted targets (out of 15 tested) were supported experimentally using a HeLa cell reporter system. The predicted regulatory targets of mammalian miRNAs were enriched for genes involved in transcriptional regulation but also encompassed an unexpectedly broad range of other functions.被引频次:2,327(来自所有数据库)Identification of novel genes coding for small expressed RNAs作者:Lagos-Quintana, Mariana; Rauhut, Reinhard; Lendeckel, Winfried; 等.Science (Washington D C)卷:294期:5543页:853-858出版年:26 October, 2001关闭摘要In Caenorhabditis elegans, lin-4 and let-7 encode 22- and 21-nucleotide (nt) RNAs, respectively, which function as key regulators of developmental timing. Because the appearance of these short RNAs is regulated during development, they are also referred to as small temporal RNAs (stRNAs). We show that many 21- and 22-nt expressed RNAs, termed microRNAs, exist in invertebrates and vertebrates and that some of these novel RNAs, similar to let-7 stRNA, are highly conserved. This suggests that sequence-specific, posttranscriptional regulatory mechanisms mediated by small RNAs are more general than previously appreciated.被引频次:2,220(来自所有数据库)CombinatorialmicroRNAtarget predictions作者:Krek, A; Grun, D; Poy, MN; 等.NATURE GENETICS卷:37期:5页:495-500出版年:MAY 2005关闭摘要MicroRNAs are small noncoding RNAs that recognize and bind to partially complementary sites in the 3 untranslated regions of target genes in animals and, by unknown mechanisms, regulate protein production of the target transcript(1-3). Different combinations of microRNAs are expressed in different cell types and may coordinately regulate cell-specific target genes. Here, we present PicTar, a computational method for identifying common targets of microRNAs. Statistical tests using genome-wide alignments of eight vertebrate genomes, PicTars ability to specifically recover published microRNA targets, and experimental validation of seven predicted targets suggest that PicTar has an excellent success rate in predicting targets for single microRNAs and for combinations of microRNAs. We find that vertebrate microRNAs target, on average, roughly 200 transcripts each. Furthermore, our results suggest widespread coordinate control executed by microRNAs. In particular, we experimentally validate common regulation of Mtpn by miR-375, miR-124 and let-7b and thus provide evidence for coordinate microRNA control in mammals.被引频次:2,094(来自所有数据库)The nuclear RNase III Drosha initiatesmicroRNAprocessing作者:Lee, Y; Ahn, C; Han, JJ; 等.NATURE卷:425期:6956页:415-419出版年:SEP 25 2003关闭摘要Hundreds of small RNAs of similar to22 nucleotides, collectively named microRNAs (miRNAs), have been discovered recently in animals and plants(1-10). Although their functions are being unravelled(1,2,11-13), their mechanism of biogenesis remains poorly understood. miRNAs

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