MOV10 RNA Helicase Is a Potent Inhibitor of Retrotransposition in Cells 英文参考文献.docVIP

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MOV10 RNA Helicase Is a Potent Inhibitor of Retrotransposition in Cells 英文参考文献.doc

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MOV10 RNA Helicase Is a Potent Inhibitor of Retrotransposition in Cells 英文参考文献

MOV10RNAHelicaseIsaPotentInhibitorof RetrotranspositioninCells JohnL.Goodier*,LingE.Cheung,HaigH.Kazazian Jr. McKusick-NathansInstituteforGeneticMedicine,JohnsHopkinsUniversitySchoolofMedicine,Baltimore,Maryland,UnitedStatesofAmerica Abstract MOV10protein,aputativeRNAhelicaseandcomponentoftheRNA–inducedsilencingcomplex(RISC),inhibitsretrovirus replication.WeshowthatMOV10alsoseverelyrestrictshumanLINE1(L1),Alu,andSVAretrotransposons.MOV10associates withtheL1ribonucleoproteinparticle,alongwithotherRNAhelicasesincludingDDX5,DHX9,DDX17,DDX21,andDDX39A. However,unlikeMOV10,theseotherhelicasesdonotstronglyinhibitretrotransposition,anactivitydependentuponintact helicasedomains.MOV10associationwithretrotransposonsisfurthersupportedbyitscolocalizationwithL1ORF1protein in stress granules, by cytoplasmic structures associated with RNA silencing, and by the ability of MOV10 to reduce endogenousandectopicL1expression.ThemajorityofthehumangenomeisrepetitiveDNA,mostofwhichisthedetritus ofmillionsofyearsofaccumulatedretrotransposition.Retrotransposonsremainactivemutagens,andtheirinsertioncan disruptgenefunction.Therefore,thehosthasevolveddefensemechanismstoprotectagainstretrotransposition,anarsenal weareonlybeginningtounderstand.Withhomologsinothervertebrates,insects,andplants,MOV10mayrepresentan ancientandinnateformofimmunityagainstbothinfectivevirusesandendogenousretroelements. Citation:GoodierJL,CheungLE,KazazianHHJr(2012)MOV10RNAHelicaseIsaPotentInhibitorofRetrotranspositioninCells.PLoSGenet8(10):e1002941. doi:10.1371/journal.pgen.1002941 Editor:HarmitS.Malik,FredHutchinsonCancerResearchCenter,UnitedStatesofAmerica ReceivedMarch7,2012;AcceptedJuly23,2012;PublishedOctober18,2012 Copyright: ? 2012 Goodier 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:ThisworkwassupportedbyanNIH/NIGMSgran