P68 RNA Helicase (DDX5) Alters Activity of Cis- and Trans-Acting Factors of the Alternative Splicing of H-Ras 英文参考文献.docVIP

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P68 RNA Helicase (DDX5) Alters Activity of Cis- and Trans-Acting Factors of the Alternative Splicing of H-Ras 英文参考文献.doc

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P68 RNA Helicase (DDX5) Alters Activity of Cis- and Trans-Acting Factors of the Alternative Splicing of H-Ras 英文参考文献

P68RNAHelicase(DDX5)AltersActivityofCis-and Trans-ActingFactorsoftheAlternativeSplicingofH-Ras MariaCamats.,SoniaGuil.¤,MarietteKokolo,MontseBach-Elias* UnidaddeSplicing,InstitutodeInvestigacionesBiome′dicasdeBarcelona-ConsejoSuperiordeInvestigacionesCient?′ficas,Barcelona,Spain Abstract Background:H-Raspre-mRNAundergoesanalternativesplicingprocesstorendertwoproteins,namelyp21H-Rasandp19 H-Ras,duetoeithertheexclusionorinclusionofthealternativeintronDexon(IDX),respectively.p68RNAhelicase(p68)is knowntoreduceIDXinclusion. PrincipalFindings:Hereweshowthatp68unwindsthestem-loopIDX-rasISS1structureandpreventsbindingofhnRNPH toIDX-rasISS1.Wealsofoundthatp68altersthedynamiclocalizationofSC35,asplicingfactorthatpromotesIDXinclusion. TheknockdownofhnRNPA1,FUS/TLSandhnRNPHresultedinupregulationoftheexpressionofthegeneencodingthe SC35-bindingprotein,SFRS2IP.Finally,FUS/TLSwasobservedtoupregulatep19expressionandtostimulateIDXinclusion, andinvivoRNAi-mediateddepletionofhnRNPHdecreasedp19H-Rasabundance. Significance:Takentogether,p68isshowntobeanessentialplayerintheregulationofH-Rasexpressionaswellasinavital transductionsignalpathwaytiedtocellproliferationandmanycancerprocesses. Citation:CamatsM,GuilS,KokoloM,Bach-EliasM(2008)P68RNAHelicase(DDX5)AltersActivityofCis-andTrans-ActingFactorsoftheAlternativeSplicingofH- Ras.PLoSONE3(8):e2926.doi:10.1371/journal.pone.0002926 Editor:JuanValcarcel,CentredeRegulacio′ Geno`mica,Spain ReceivedJune17,2008;AcceptedJuly18,2008;PublishedAugust13,2008 Copyright: ? 2008 Camats et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:ThisworkwassupportedbyFundacio′ndeInvestigacio′nMe′dica Mu′tuaMadrilen?aAutomovilista(Fundacio′nMMA)andbythePlanNacional(MEC) BFU2005-00701.M.C.,S.GandM.K.wererecipientsofaFmedMMA,BEFI(CarlosIII)andFPU(MEC)fellowships,respectively.Th