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1、Topic5microRNAsandCellFatemicroRNAs和细胞命运microRNAs(miRNAs)1993年发现于Caenorhabditiselegans,近年才被重视2002年Science年度评选10大科学成就高居榜首~21-24nt的小分子非编码RNA通过对RNA的裂解或翻译抑制起到基因调控的作用参与细胞生长与分化、生长发育、肿瘤形成和抑制miRNAs作用机制1.降解mRNA：植物中多见2.抑制mRNA的翻译：动物众多见miRNAs通过不完全的碱基配对结合mRNA的3’非翻译区（UTRs）转录后水平上抑制基因翻
2、译仅降低其靶基因的蛋白质表达不影响mRNA水平miRNAs的生物合成过程RNA聚合酶II(PolII)转录合成Pri-miRNARNaseIIIDrosha和双链RNA结合蛋白Pasha处理成约小片段的的pre-miRNAexportin5将这种前体分子输送到细胞质中RNaseIIIDicer剪切产生约22nt的miRNA双链被整合到miRISC复合体中miRNAs调节多个靶基因miRNAs和其结合位点非完全互补的，存在短的错配和G–U配对同一家族的成熟miRNAs在5’末端具有高度的同源性miRNA的5’末端：对于miRNA进入mi
3、RISC及其其生物学功能相当关键“miRNAseed”搜索：利用一个包含了成熟miRNA的2-8位的碱基序列的miRNAseed”来搜索所有基因的3’非编码区域的互补序列一个单独的miRNA可以结合多达200个靶基因单个基因的3’非翻译区域具有几个miRNAs的结合位点miRNAbiogenesisanditsregulationTechnologytostudyfunctionofmiRNAsmiRNAsoverexpressionDicer/DGCR8knockdown+rescueCoupling transcriptional
4、 and post‐transcriptional miRNA regulation in the control of cell fateIncancercells,inactivationofthemiRNA-mediatedsilencingpathwayandtheavoidanceofmiRNAregulationcontributetotransformation.(A)miRNAs and TFs in FFLs tend to mutually target genes from the same pathway. (
5、B) Additionally, co‐regulated miRNAs and miRNAfamilies co‐target many genes in the same pathway, thus resulting in a significant total output, having a major effect on cell fate.Different ways by which FFLs can account for the enhanced phenotypic effect of miRNAs on cel
6、l fate"miRNA‐target spatiotemporal avoidance"MicroRNAsinEmbryonicStemCellsAtotalof678and472miRNAgeneshavebeendiscoveredinthehumanandmousegenomes,respectively,butonlyasubsetofthesemiRNAsisexpressedinESCs.Fewerthan100miRNAswereinitiallyidentifiedinhumanormurineEScellsbycl
7、oningandsequencingfromsmallRNAlibraries.Inindependentstudies,differentEScelllinesshowdistinctmiRNAprofiles.hsa-let-7a,hsa-miR-103,hsa-miR-130a,hsa-miR-136,hsa-miR-143,hsa-miR-151,hsamiR-16,hsa-miR-17,hsa-miR-200c,hsa-miR-21,hsa-miR-221,hsa-miR-222,hsa-miR-26a,hsa-miR-28
8、,hsa-miR-29b,hsa-miR-301,hsa-miR-302a,hsa-miR-302b,hsa-miR-302c,hsa-miR-302d,hsa-miR-320,hsa-miR-367,hsa-miR-3
