RNA-ligand interactions and control of gene expression.ppt

RNA-ligandinteractionsandcontrolofgeneexpressionOutline• RNAinterference(microRNAsandsiRNAs)• RibosomalRNA,tRNA,andmRNAinteractions• RNAinteractionsaffectingtranslationandtranscription(outsidetheribosome)• NakedRNA• RNA-metaboliteinteractions(riboswitches)RNAinterferenceRNAinterference(RNAi)• RNAiistheprocesswherebydouble-strandedRNA(dsRNA)induceshomology-dependentdegradationofcognateRNA()• RNAiiscentraltocellularmechanismsofpost-transcriptionalgenesilencing(PTGS)andcanalsoeffecttranscriptionalgenesilencing(TGS)• RNAiishighlyconservedamongeukaryotes(fungi,protozoans,plants,nematodes,invertebrates,mammals)• Double-strandedRNA(dsRNA)isprocessedbyDicer,anRNaseIIIfamilymember,toproduce21-23ntsmallinterferingRNAs(siRNAs)• ponentnucleasecalledtheRNA-plex(RISC).• ponentsoftheRNAipathway• Dicer DicerbelongstotheRNaseIIIfamilyofdsRNA--bindingmotifsandaPAZdomainbelievedtomediateprotein-proteininteractions.• Argonautehomologs(Dicer/RISCassociated) .• RNA-dependentRNApolymerase(RdRP) EndogenousRdRPsinfluenceRNAiincertaineukaryotesincludingfungi,plants,• • ItwasobservedthatantisenseorsenseRNAcouldequallyeffectsilencing(knock-down)oftargetgeneexpression• bined(dsRNA)is10-timesmoreeffectiveinsilencingtargetgeneexpression• • AnymeansbywhichsiRNAscanbegeneratedanddeliveredtoacellcanelicitRNAiandgene-specificsilencing• siRNAsarepowerfultoolsformanipulatinggeneexpressionanddetermininggenefunctionNaturedidnotexhaustbillionsofyearsofevolutiononRNAisolelyforthebenefitofmoderndaybiologists!