mRNA选择性剪接的分子机制

©1994-2010ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.(1):102107ISSN0379-4172:2003-04-07;:2003-07-31:(1970-),,:E2mail:[e-mail]RNAAlternativeSplicingZHANGGuo2Wei,SONGHuai2Dong,CHENZhu(ShanghaiInstituteofHematology,RuijinHospital,Shanghai200025,China)Abstract:Eukayoticpre2mRNAsaresplicedtoformmaturemRNA.Thepre2mRNAsalternativesplicinggreatlyincreasesthedi2versityofproteinsandthecomplexityofgenesexpression.Therecognitionofsplicesitescanoccuracrossintron(introndefinition)oracrossexon(exondefinition).Therearemanykindsofalternativesplicingpatterns,includingthechoiceofalternativesplicingsites,thechoiceofalternativesplicingends,thealternativesplicingofmutuallyexclusiveexons,andanintroncanbeexcisedfromorretainedinmRNA.Thesplicesiteschoiceprocessisregulatedbymanykindsofcis2actingandtrans2actingelementsandiscloselyrelatedwiththebasicsplicingprocess.Someofthesplicingfactorsinbasicsplicingprocesscanregulatethealternativesplicing.Thealternativesplicingisalsoaco2transcriptionalprocess.Promoterscanregulatealternativesplicingandproducediffer2entmRNAisoforms.Manymolecularmechanismsofalternativesplicinghavebeenproposed,anditwasalsofoundthattheRNAed2itingandtrans2splicingcouldalsoregulatealternativesplicing.Keywords:mRNA;alternativesplicingmRNA,,(,200025):mRNAmRNA,mRNA,()():,,,,1,mRNA,RNA:mRNA;:Q522:A:037924172(2004)0120102206,,DNARNA,mRNA[13]Modrek[1]EST35%59%,70%88%,,©1994-2010ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.[4]U1snRNP5SF1(splicingfactor1)U2snRNP3,U2snRNPU2AF,U2AF65kDa35kDa,U2AF65,U2AF353AG,U2snRNP,U5U4P6snRNP,[5]2,,,,50300,,,3365,,,(introndefinition);,35(exondefi2nition)[6],,(exonskipping),[2,3]:53(1,ab);53(1,cd);(1,e);(1,f);mRNA(1,g),Dscam38000,1mRNAFig.1PatternsofmRNAalternativesplicing3,,,()():,,,,(exonsplicingenhancer,ESE)doublesex(dsx)ESE,3[7,8]Tra,Tra2SR301ZHANGGuo2Weietal.:MolecularMechanismofmRNAAlternativeSplicing©1994-2010ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.(2,a)5,fruitless,5,,Tra,Tra2SRESEU15(2,b),ESE53[9]SRESERNA12RNA(RRM),CRSRRMSRRNA,RS,SRU1snRNPU2AF,U1snRNPU2AF,SRESE,U2AF3U1snRNP5,Src1(intronsplicingenhancer,ISE),ESE[3],Li[10]5,9415%15,,5,1mRNA2ESE[4]Fig.2ModelsforsplicingactivationbyESE,,,[7]P15,U1snRNP,5U1snRNP,[3]caspase22mRNA,100(IN100),3,,,,[11],hnRNP,hnRNPmRNAhnRNPA1mRNA,U1snRNP5,5SRhnRNPAPBU2AF[12]SRSF2PASFhnRNPA1mRNA,hnRNPA1mRNA,U1snRNP5,5SF2PASFhnRNPA15ESESR(exonsplicingsilencer,ESS)hnRNP(PTB),U2AF,3PTB5,[7,8,12]SXL(sex2lethal)1hnRNP,,SXLtramRNA31,U2AF3,TRA,4,mRNA[12,15],RNA401ActaGeneticaSinicaVol.31No.12004©1994-2010ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.(CTD)mRNACTDmRNA5,mRNACTDSRmRNAFong[16],UsnRNPTAT2SF1RNA,mRNA[14,17],,,;,[1518]Cceres[12]:(3,ab),X,YRNA,X,YSRCTD,Y,;RNA(3,cd),XRNA,3,YRNA,3,3Fig.3Modelsofalternativesplicingcontrolledbypromoter501ZHANGGuo2Weietal.:MolecularMechanismofmRNAAlternativeSplicing©1994-2010ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.(CBC)53,mRNA,mRNA3UTR3[22]:(1)(3,a),3UTR;(2)(3,b),151,5,,,;(3)(3,c),5,3[23],13BhnRNPFCstF264IgmRNA[24]4mRNA3Fig.4Modelsforalternativepoly(A)siteselection6GC2AGGT2AG,,GC2AGThanarajTAFrancisClark[25](ESTmRNA),015%GC2AG,5%GC2AG,62%GC2AGGCGT,,GC2AGU1U5PU6snRNA,,,,AG,U2AF35,GC2AG7RNARueterSM[26]1999RNAADAR2mRNAADAR21RNA,mRNA,ADAR2mRNA1,ADAR247,AAAG,ADAR2AAAI,AIAG,RNA8mRNA4P4503A:CYP3A4CYP3A5CYP3A7CYP3A43,,13,,FintaCZaphiro2poulosP[27]CYP3AmRNA,CYP3A43CYP3A4CYP3A5CYP3A43CYP3A4CYP3A5,601ActaGeneticaSinicaVol.31No.12004©1994-2010ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.[28],,,,(References):[1]BarmakModrek,andChristopherLee.Agenomicviewofalternativesplicing.NatureGenetics,2002,30:1319.[2]SusanM.Berget.Exonrecognitioninvertebratesplicing.JBiolChem,1996,270:24112414.[3]BrentonR.Graveley.Alternativesplicing:increasingdiversityintheproteomicworld.TrendsGenet,2001,17:100107.[4]DouglasL.Black.Mechanismsofalternativepre2messengerRNAsplicing.AnnuRevBiochem,2003,72:291336.[5]AJavierLopez.Alternativesplicingofpre2mRNA:developmentalcon2sequencesandmechanismsofregulation.AnnuRevGenet,1998,32:279305.[6]ChristopherWJSmith,JuanValcrcel.Alternativepre2mRNAsplic2ing:thelogicofcombinatorialcontrol.TrendsBiochemSci,2000,25:381388.[7]BiancaJLam,KlemensJHertel.Ageneralroleforsplicingenhancersinexondefinition.RNA,2002,8:12331241.[8]BinghuiLi,ChaimWachtel,ElanaMiriami,GalitYahalom,GilgiFriedlander,GilSharon,RuthSperling,andJosephSperling.Stopcodonsaffect5splicesiteselectionbysurveillanceofsplicing.ProcNatlAcadSciUSA,2002,99(8):52775282.[9]JocelynCÉt,SophieDupuis,Zhi2HongJiang,JaneYWu.Caspase22pre2mRNAalternativesplicing:Identificationofanintronicelementcontainingadecoy3acceptorsite.ProcNatlAcadSciUSA,2001,98(3):938943.[10]JavierF.Cceres,AlbertoR.Kornblihtt.Alternativesplicing: