SnapShot:PosttranscriptionalGeneSilencingSigalPressman,YanxiaBei,andRichardCarthewDepartmentofBiochemistry,MolecularBiologyandCellBiology,NorthwesternUniversity,Evanston,IL60208,USA570Cell130,August10,2007©2007ElsevierInc.DOI10.1016/j.cell.2007.07.042Seeonlineversionforlegend,abbreviations,andreferences.(A)siRNA-MediatedPosttranscriptionalGeneSilencingDouble-strand(ds)RNAsthataretakenupexogenously,formedduringviralreplication,orgeneratedfromaberrantcellularRNAsarecutinto21–23nucleotide(nt)siRNAsbyDicerinassociationwithdsRNA-binding(dsRBD)protein.ThesiRNAsarethenloadedintoRISC,acomplexcontainingArgonaute(Ago)protein.Afterelimi-nationofthesiRNApassengerstrand,RISCpairswithcognateRNAviathesiRNAguidestrandandcutsitstargetusingthesliceractivityofAgo.InmammalsandDrosophilathecleavedtargetisthendegraded.Inplants,C.elegans,andfungi—whosegenomesencodeRNA-dependentRNApolymerase(s)(RdRPorRDR)—thecleavedtargetRNAservesastemplateforRdRPtogeneratemoredsRNAsthatwillbedicedintosecondarysiRNAs.ThesesecondarysiRNAs,whichinC.elegansarerecognizedbySAGO(syntheticsecondary-siRNAdefectiveAgo),furtherdownregulatetargetRNAs.(B)miRNA-MediatedPosttranscriptionalGeneSilencingB1:AnimalmiRNAbiogenesis.RNApolymeraseIItranscribesmicroRNAgenesasprimarymiRNAs(pri-miRNAs)thatfoldbacktoformastem-loopstructure.Animalpri-miRNAsarecleavedinthenucleusbytheRNaseIIIenzymeDroshaanditsdsRBDproteinpartnerinto50–80ntprecursormiRNAs(pre-miRNAs).Pre-miRNAsarethenactivelyexportedbyExportin5tothecytoplasm,wheretheyundergoasecondcleavagebytheDiceranditsdsRBDproteinpartner.Theresulting~21ntduplex,containingthematuremiRNAstrandandthepassengermiRNA*strand,isunwoundandthematuremiRNAstrandisincorporatedintoamicroribonucleoprotein(miRNP)complex,containinganAgoprotein.Recently,asecondpathwayforgeneratingmiRNAswasidentifiedinC.elegansandDrosophila,whereshortintronsaresplicedandde-branched,yieldingpre-miRNA-likehairpinstermedmirtrons.BypassingDroshacleavage,themirtronpathwayisthoughttomergewiththecanonicalmiRNApathwa...
