医用分子遗传学转录和转录后修饰

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1、李希分子医学教育部重点实验室lixi@shmu.edu.cnTranscriptionandPost-transcriptionModificationPost-transcriptionalProcessingofRNAMakingendsofRNARNAsplicingPrimaryTranscriptPrimaryTranscript-theinitialmoleculeofRNAproduced---hnRNA（heterogenousnuclearRNA）Inprokaryotes,DNA→RNA→proteinincytoplasmcon

2、currentlyIneukaryotesnuclearRNA>>CpRNAProcessingofeukaryoticpre-mRNAHumandystrophingenehas79exons,spansover2,300-Kbandrequiresover16hourstobetranscribed!Forprimarytranscriptscontainingmultipleexonsandintrons,splicingoccursbeforetranscriptionofthegeneiscomplete--co-transcriptiona

3、lsplicing.TypesofRNAprocessingA)Cuttingandtrimmingtogenerateends:rRNA,tRNAandmRNAB)Covalentmodification:AddacapandapolyAtailtomRNAAddamethylgroupto2’-OHofriboseinmRNAandrRNAExtensivechangesofbasesintRNAC)Splicingpre-rRNA,pre-mRNA,pre-tRNAbydifferentmechanisms.TheRNAPolIICTDisreq

4、uiredforthecouplingoftranscriptionwithmRNAcapping,polyadenylationandsplicingThecouplingallowstheprocessingfactorstopresentathighlocalconcentrationswhensplicesitesandpoly(A)signalsaretranscribedbyPolII,enhancingtherateandspecificityofRNAprocessing.Theassociationofsplicingfactorsw

5、ithphosphorylatedCTDalsostimulatesPolIIelongation.Thus,apre-mRNAisnotsynthesizedunlessthemachineryforprocessingitisproperlypositioned.TimecourseofRNAprocessing5’and3’endsofeukaryoticmRNAAddaGMPMethylateitand1stfewnucleotidesCutthepre-mRNAandaddA’s5’-UTR3’-UTRCappingofpre-mRNAsCa

6、p=modifiedguaninenucleotideCapping=firstmRNAprocessingevent-occursduringtranscriptionCTDrecruitscappingenzymeassoonasitisphosphorylatedPre-mRNAmodifiedwith7-methyl-guanosinetriphosphate(cap)whenRNAisonly25-30bplongCapstructureisrecognizedbyCBC（cap-bindingcomplex）stablizethetrans

7、criptpreventdegradationbyexonucleasesstimulatesplicingandprocessingSometimesmethylatedSometimesmethylatedThecapisaddedafterthenascentRNAmoleculesproducedbyRNApolymeraseIIreachalengthof25-30nucleotides.GuanylyltransferaseisrecruitedandactivatedthroughbindingtotheSer5-phosphorylat

8、edPolIICTD.ThemethylgroupsarederivedfromS-adeno