novel regulators of gene expression and genome integrity课件

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1、THEFAMILYOFSMALLNON-CODINGRNAs“silencing”NovelregulatorsofgeneexpressionandgenomeintegrityInhibitionoftranslationofmRNAintoproteinDegradationofmessengerRNAsGenomedefenders(Virus-Transposons)ChromatineorganizationBREAKTHROUGHOFTHEYEAR(December2002)SMALLRNAs:REGULATORSANDGUARDIANSOFTHEGENOMETHEFA

2、MILYOFNON-CODINGRNAspiRNAsmiRNAssiRNAsTHEYCOLLECTIVELYFUNCTIONASSEQUENCE-SPECIFICGUIDESTOSILENCEORREGULATEGENES,TRANSPOSONS,ANDVIRUSESANDTOMODIFYCHROMATINANDGENOMESTRUCTURE.(PIWI-ASSOCIATED)(MICRORNA)(SHORTINTERFERINGRNA)~21nt~21nt~30ntSmallnon-codingRNAsLongnon-codingRNAs20-35nt(TelomeraseRNA)

3、500nt17kb108kb(HumanXist)(mouseAirRNAs)(siRNA,piRNA,miRNA)Thesmallnon-codingRNAgroupTHESMALLINTERFERINGRNAs--THEGENOME’SIMMUNESYSTEM--Natureabhorsdouble-strandedRNA.Whenconfrontedwithdouble-strandedRNA(dsRNA),eukaryoticcellsrespondeliminatingtheirownmRNAsthatsharesequenceswiththedoublestrand.So

4、urcesofsiRNAaredsRNAthataretypicallyhundredsofbasepairlong(viral-ortransposon-derivedreplicationintermediates).piRNAmiRNAsiRNASmallRNAsFire,A.etal.Potentandspecificgeneticinterferencebydouble-strandedRNAinCaenorhabditiselegans.Nature391,806–811(1998).THESMALLINTERFERINGRNAs(siRNA)CraigMelloAndr

5、ewFireNobelPrize2006inPhysiologyandMedicineRNAiwasfirstdiscoveredinC.elegansasaresponsetoexogenousdsRNApiRNAmiRNAsiRNASmallRNAsRNA-INDUCEDSILENCINGCOMPLEXdsRNA-specificRNaseIII(Dicer)GuidestrandBiogenesisofEffectorsiRNAspiRNAmiRNAsiRNASmallRNAsPassengerstrandsiRNAsENDOgenousEXOgenousnatsiRNAs(n

6、atural)tasiRNAs(trans-acting)TransgenesVirusEXO-ANDENDO-SMALLINTERFERINGRNAsRNAicanbeelicitedexogenously,bydsRNAsuppliedfromoutsidethecell,orendogenously,fromtranscriptionofcodingornoncodinggenomicsequencespiRNAmiRNAsiRNASmallRNAscasiRNAs(cis-acting)PlantswormsTransposons,repetitiveelementsHete

7、rochromatinformationbyDNAmethylation,histonemodificationTranscript(mRNA)cleavageTranscript(mRNA)cleavage(stressreponses)FliesMammalsEndo-siRNAsDerivedfromtransposons,heterochromaticsequences,intergenicregions,mRNAsTranscriptcleava