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1、Topic5microRNAsandCellFatemicroRNAs和細(xì)胞命運(yùn)microRNAs(miRNAs)1993年發(fā)現(xiàn)于Caenorhabditiselegans,近年才被重視2002年Science年度評(píng)選10大科學(xué)成就高居榜首~21-24nt的小分子非編碼RNA通過對(duì)RNA的裂解或翻譯抑制起到基因調(diào)控的作用參與細(xì)胞生長與分化、生長發(fā)育、腫瘤形成和抑制miRNAs作用機(jī)制1.降解mRNA：植物中多見2.抑制mRNA的翻譯：動(dòng)物眾多見miRNAs通過不完全的堿基配對(duì)結(jié)合mRNA的3’非翻譯區(qū)（UTRs）轉(zhuǎn)錄后水平上抑制基因翻
2、譯僅降低其靶基因的蛋白質(zhì)表達(dá)不影響mRNA水平miRNAs的生物合成過程RNA聚合酶II(PolII)轉(zhuǎn)錄合成Pri-miRNARNaseIIIDrosha和雙鏈RNA結(jié)合蛋白Pasha處理成約小片段的的pre-miRNAexportin5將這種前體分子輸送到細(xì)胞質(zhì)中RNaseIIIDicer剪切產(chǎn)生約22nt的miRNA雙鏈被整合到miRISC復(fù)合體中miRNAs調(diào)節(jié)多個(gè)靶基因miRNAs和其結(jié)合位點(diǎn)非完全互補(bǔ)的，存在短的錯(cuò)配和G–U配對(duì)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：對(duì)于miRNA進(jìn)入mi
3、RISC及其其生物學(xué)功能相當(dāng)關(guān)鍵“miRNAseed”搜索：利用一個(gè)包含了成熟miRNA的2-8位的堿基序列的miRNAseed”來搜索所有基因的3’非編碼區(qū)域的互補(bǔ)序列一個(gè)單獨(dú)的miRNA可以結(jié)合多達(dá)200個(gè)靶基因單個(gè)基因的3’非翻譯區(qū)域具有幾個(gè)miRNAs的結(jié)合位點(diǎn)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
