Gene-X-ppt(Gene10-基因十)--Chapter30

Chapter30RegulatoryRNA30.1Introduction•RNAfunctionsasaregulatorbyformingaregionofsecondarystructure(eitherinter-orintramolecular)thatchangesthepropertiesofatargetsequence.FIGURE01:RegulatorRNAbindsRNAtarget30.2ARiboswitchCanAlterItsStructureAccordingtoItsEnvironment•AriboswitchisanRNAwhoseactivityiscontrolledbythemetaboliteproductoranothersmallligand(aligandisanymoleculethatbindstoanother).•Ariboswitchmaybearibozyme.•aptamer–AnRNAdomainthatbindsasmallmolecule;thiscanresultinaconformationchangeintheRNA.FIGURE02:GlcN6PactivatesaribozymethatcleavesthemRNA30.3NoncodingRNAsCanBeUsedtoRegulateGeneExpression•Vasttractsoftheeukaryoticgenomearetranscribed.•antisensegene–Agenethatcodesforan(antisense)RNAthathasacomplementarysequencetoanRNAthatisitstarget.•antisenseRNA–RNAthathasacomplementarysequencetoanRNAthatisitstarget.FIGURE04:TranscriptionofantisenseRNAgeneratesanRNA-RNAduplex30.3NoncodingRNAsCanBeUsedtoRegulateGeneExpression•AregulatorRNAcanfunctionbyformingaduplexregionwithatargetRNA.•Theduplexmayblockinitiationoftranslation,causeterminationoftranscription,orcreateatargetforanendonuclease.•Transcriptionalinterference(TI)occurswhenanoverlappingtranscriptonthesameoroppositestrandpreventstranscriptionofanothergene.30.3NoncodingRNAsCanBeUsedtoRegulateGeneExpression•nestedgene–Agenelocatedwithinanintronofanothergene.•NoncodingRNAs(ncRNA)(suchasCUTsandPROMPTs)areoftenpolyadenylatedandveryunstable.FIGURE05:AntisenseRNAregulatesgeneexpression.AdaptedfromJ.Camblong,etal.,Cell131(2007):706-717.30.4BacteriaContainRegulatorRNAs•BacterialregulatorRNAsarecalledsRNAs.•SeveralofthesRNAsareboundbytheproteinHfq,whichincreasestheireffectiveness.•TandemrepeatscanbetranscribedintopowerfulantiviralRNAs.30.4BacteriaContainRegulatorRNAs•TheoxySsRNAactivatesorrepressesexpressionof10lociattheposttranscriptionallevel.FIGURE06:oxySiscontrolledbyoxyRandH2O2ReprintedfromCell,vol.90,S.Altuvia,etal.,AsmallstableRNA...,pp.43-53.Copyright1997,withpermissionfromElsevier[].PhotocourtesyofGiselaStorz,NationalInstitutesofHealth.FIGURE07:A3’terminalloopinoxySRNApairswiththeinitationsiteofflhAmRNA30.4BacteriaContainRegulatorRNAs•CRISPR–ClustersofregularlyinterspersedshortpalindromicrepeatsinprokaryotesthataretranscribedandprocessedintoshortRNAsthatfunctioninRNAinterference.FIGURE08:TheCRISPRlocusinE.coliistranscribedintoalargerprecursorRNAReproducedfromR.F.YoungIII,Science321(2008):922-923[].ReprintedwithpermissionfromAAAS.30.5MicroRNAsAreWidespreadRegulatorsinEukaryotes•Eukaryoticgenomescodeformanyshort(~22base)RNAmoleculescalledmicroRNAs(miRNAs).•RNAinterference(RNAi)–Aprocessbywhichshort(21to23)nucleotideantisenseRNAs,derivedfromlongerdouble-strandedRNAs,canmodulateexpressionofmRNAbytranslationinhibitionordegradation.30.5MicroRNAsAreWidespreadRegulatorsinEukaryotes•stRNA–ShorttemporalRNA;aformofmiRNAineukaryotesthatmodulatesmRNAexpressionduringdevelopment.•piRNAsregulategeneexpressioningermcellsandacttosilencetransposableelements.•siRNAsarecomplementarytovirusesandtransposableelements.30.5MicroRNAsAreWidespreadRegulatorsinEukaryotes•Drosha–Anendonucleasethatprocessesdouble-strandedprimaryRNAsintoshort,~70basepairprecursorsforDicerprocessing.•Dicer–Anendonucleasethatprocessesdouble-strandedprecursorRNAto21to23nucleotideRNAimolecules.30.5MicroRNAsAreWidespreadRegulatorsinEukaryotes•RISC–RNA-inducedsilencingcomplex,aribonucleoproteinparticlecomposedofashort,single-strandedsiRNAandanucleasethatcleavesmRNAscomplementarytothesiRNA.–ItreceivessiRNAfromDiceranddeliversittothemRNA.30.5MicroRNAsAreWidespreadRegulatorsinEukaryotes•rasiRNA–Repeat-associatedsilencerRNAisagermlinesubsetofmiRNAtranscribedfromtransposableelementsandotherrepeatedelementsthatareusedtosilencethem.30.6HowDoesRNAInterferenceWork?•MicroRNAsregulategeneexpressionbybasepairingwithcomplementarysequencesintargetmRNAs.•RNAinterferencetriggersdegradationortranslationinhibitionofmRNAscomplementarytomiRNAorsiRNA.–ItcanalsoleadtomRNAactivation.30.6HowDoesRNAInterferenceWork?FIGURE11:MechanismsofmiRNA-mediatedgenesilencingReprintedfromCell,vol.132,A.Eulalio,E.Huntzinger,andE.Izaurralde,GettingtotheRootofmiRNA...,pp.9-14.Copyright2008,withpermissionfromElsevier[].30.6HowDoesRNAInterferenceWork?FIGURE12:lin14codesforasingleprotein30.6HowDoesRNAInterferenceWork?•dsRNAmaycausesilencingofhostgenes(RNAsilencing).FIGURE13:dsRNAhasbothgeneralandspecificeffects30.7HeterochromatinFormationRequiresMicroRNAs•MicroRNAscanpromoteheterochromatinformation.•RNA-dependentRNApolymerase(RDRP)–AcomponentoftheRITScomplexthatcopiestheheterochromatinncRNAthatisthenusedtosilenceheterochromatintranscription.•RITS(RNA-inducedtranscriptionalsilencing)–Acomplexthatusesshortsingle-strandedsiRNAtorepressheterochromatintranscription.30.7HeterochromatinFormationRequiresMicroRNAsReprintedfromCell,vol.130,Y.Bei,S.Pressman,andR.Carthew,SnapShot:SmallRNA-Mediated...,pp.756.e1-756.e2.Copyright2007,with