真核生物mRNA降解途径

ISSN100727626CN1123870PQChineseJournalofBiochemistryandMolecularBiology20081024(10):883889mRNA1),1),2)3(1);2),310058)mRNA.,mRNA,mRNA.mRNA,mRNA..;;mRNA;Q522EukaryoticmRNADecayPathwaysLIULi2Ming1),XUZheng2Ping1),2)3(1)InstituteofEnvironmentalMedicine;2)ResearchCenterforEnvironmentGenomics,SchoolofMedicine,ZhejiangUniversity,Hangzhou310058,China)AbstractIneukaryote,themRNAdegradationplaysanimportantroleingeneexpressionregulation.Uptodate,manyenzymesandproteincomplexhavebeenidentifiedtobeinvolved.Aspecificcytoplasmicstructure,P2body,hasbeenproposedasthemainsiteformRNAdegradation.Inthisreview,wewilloutlinethedifferentmRNAdegradationpathwaysandthefunctioninvolvedinenzymesandfactors,andwillfocusontheroleofP2bodyintheprocessofmRNAdegradation.Finally,wewilldisscusstheprospectsandissuestothisresearchfield.Keywordseukaryote;geneexpression;mRNAdecay;P2body:2008203203;:2008206230([2007]191)3Tel:[phone];E2mail:[e-mail]:March3,2008;Accepted:June30,2008SupportedbyZhejiangProvincialProgramforCultivationofHigh2LevelInnovativeHealthTalents(No.20072191)3CorrespondingauthorTel:0571288208008;E2mail:[e-mail],mRNA,,Dcp1p[1]Pat1p[2]Rap55[3]staufen[4].,,mRNA[5,6].,(P2body)mRNAmRNA.mRNA,mRNA:.mRNA,3,mRNAmRNAmRNA,mRNA.,,3,mRNA(nonsense2mediatedmRNAdecay,NMD)NSD(non2stopdecay)NGD(no2godecay).,mRNA,mRNA.mRNA,,1mRNA,mRNA.1mRNA1.1mRNAmRNA572(m7Gppp)3poly(A),eIF4EPABP(poly(A)2bindingprotein),.mRNA,.mRNApoly(A),poly(A)1015,.Fig11(886),PABPpoly(A),Dcp1:Dcp2,mRNA5m7Gppp,mRNA53[7].Dcp1:Dcp2,3mRNA35[8].2mRNA,mRNA.11111mRNA,.,PAN22PAN3CCR42NOTPARN(poly(A)2specificribonuclease).PAN22PAN3PABPPoly(A),(Saccharomycescerevisiae)mRNApoly(A)6080nt,2poly(A)200nt80nt[9].CCR42NOT,91,Ccr4Caf1[10],,CCR42NOTPAN22PAN32poly(A)[9].PARN,(cap2bindingprotein).(Xenopuslaevis),PARNmRNA.,PARN.PARN,(Drosophilamelanogaster)PARN[11].1111235mRNA35,35.6,1012,635,1PH,RNA[12].mRNA,RNAs3.35,5DcpS[13].111135335mRNA,53mRNA.,Dcp1Dcp2,Dcp2MutT[14].,Lsm17mRNA3,mRNA[15,16].EdcDhh1Pat1[17].Lsm,EDC3PABP2bindingprotein21(Pbp1)RAP55[3](RNA2associatedproteinof55kD)mRNA53.,Xrn153mRNA.1.2mRNAmRNA.,mRNA3:RPS28B[19]EDC1[20]amastin[21],Fig12.,RPS28BmRNA3UTR,EDC3RPS28BmRNA.EDC1mRNAEdc1,EDC1mRNA3UTRPoly(U)Poly(A),.,EDC1mRNACCR42NOT.,,(Lershmania)amastinmRNAUREmRNA.Fig.2Deadenylation2independentmRNAdecay[18]1.3mRNAmRNA,Fig13.,PMR1IRE1RNase48824MRP,mRNA[22].PMR1,2,mRNA.PMR1,mRNA[23].IRE1XBP1mRNA,PMR1mRNA[24].RNaseMRPRNA,rRNAmtRNA.,RNaseMRPCLB2mRNA,CLB2mRNA5UTR,3Xrn1.,,IRE1PMR1,RNaseMRP,,,3RNaseMRP[25].,3Xrn153,535.Fig.3Endonuclease2mediatedmRNAdecay[18]2mRNA2.1mRNAmRNA,DNAmRNA,mRNA.mRNAmRNA,mRNA,Fig.4(886).NMD,UPF1UPF2UPF3.,(exonjunctioncomplex,EJC),,2024.PTC(prematuretranslationterminationcodon)mRNA,EJCPTCmRNA,.,mRNA.,,EJC,poly(A)mRNA,3UTRPTCpoly(A),mRNP[26].NMD,UPF1.,(peptide2releasefactor)eRF1eRF3.PTC,,.UPF1SMG1,SURF[27].,UPF1UPF22EJC,SURFEJC.,SMG1UPF1,eRF1eRF3.,SMG7mRNA[28].NMD,.PTCmRNA,mRNA[29]ARF1mRNA[30],UPF1.mRNA,UPF1,3UTRSLBP(stem2loop2bindingprotein).ARF1mRNA,UPF1,3UTRStaufen.NMD,NMDUPF2UPF3.2.2NSDNSDmRNAmRNA,Fig15.,poly(A),NSD.,NSD.,NSD.NSD,SKISki7.3,Ski7CA,Ski7SKI,35[31,32].,58810:mRNAFig.1Deadenylation2dependentmRNAdecay[18]Fig.4Nonsense2mediateddecay[18]Fig.6No2godecay[18]Fig.5Non2stopdecay[18]68824Ski7,NSD.NSDPABP,,,mRNA53[33].2.3NGDNGDmRNA,,Fig16.NGDmRNA,mRNA,mRNA,mRNAXrn1.NGD,,.,Dom34Hbs1,eRF1eRF3,.NSDSki7,,NGDHbs13[34].3,mRNAmRNPs,,.,,mRNA.,3.1,mRNA,Dcp1p[1]Dcp2p[35]Dhh1p[35]Pat1p[2]Lsm17p[36]Edc3p[37]RAP55[3];2miRNARNANMD,argonautes[1]AIN21[38]staufen[4]TTP[37]SMG27[28];3,APOBEC3G[39]APOBEC3F[39]PKR[40]Dcs2p[41].mRNA,,,mRNP,.,miRNARISCmRNA,mRNA,mRNA[38].4,mRNA,mRNPs,.,mRNA,mRNA.,mRNA,,[39,40],,RNA,,,RNA.,mRNA,mRNPs2.,mRNA,,5[42]3.,mRNA3:,mRNA;,;,mRNA.(References)[1]Behm2AnsmantI,RehwinkelJ,DoerksT,etal.mRNAdegradationbymiRNAsandGW182requiresbothCCR4:NOTdeadenylaseandDCP1:DCP2decappingcomplexes[J].GenesDev,2006,20(14):188521898[2]ChowdhuryA,MukhopadhyayJ,TharunS.ThedecappingactivatorLsm1p27p2Pat1pcomplexhastheintrinsicabilitytodistinguishbetweenoligoadenylatedandpolyadenylatedRNAs[J].RNA,2007,13(7):99821016[3]TanakaKJ,OgawaK,TakagiM,etal.RAP55,acytoplasmicmRNPcomponent,repressestranslationinXenopusoocytes[J].JBiolChem,2006,281(52):40096240106[4]KimYK,FuricL,ParisienM,etal.Staufen1regulatesdiverseclassesofmammaliantranscripts[J].EMBOJ,2007,26(11):267022681[5]BrenguesM,ParkerR.AccumulationofpolyadenylatedmRNA,Pab1p,eIF4E,andeIF4GwithP2bodiesinSaccharomycescerevisiae[J].MolBiolCell,2007,18(7):259222602[6]BeckhamC,HillikerA,CzikoAM,etal.TheDEAD2boxRNAhelicaseDed1paffectsandaccumulatesinSaccharomycescerevisiaeP2bodies[J].MolBiolCell,2008,19(3):984299378810:mRNA[7]LongRM,McNallyMT.mRNAdecay:x(XRN1)marksthespot[J].MolCell,2003,11(5):112621128[8]vanDijkEL,SchildersG,PruijnGJ.Humancellgrowthrequiresafunctionalcytoplasmicexosome,whichisinvolvedinvariousmRNAdecaypathways[J].RNA,2007,13(7):102721035[9]YamashitaA,ChangTC,YamashitaY,etal.Concertedactionofpoly(A)nucleasesanddecappingenzymeinmammalianmRNAturnover[J].NatStructMolBiol,2005,12(12):105421063[10]WagnerE,