siRNA Has Greatly Elevated Mismatch Tolerance at 3′-UTR Sites 英文参考文献.docVIP

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siRNA Has Greatly Elevated Mismatch Tolerance at 3′-UTR Sites 英文参考文献.doc

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siRNAHasGreatlyElevatedMismatchToleranceat39- UTRSites NaWei1,LeiZhang1,HuangHuang1,YueChen2,JieZheng1,XiaoZhou1,FanYi1,QuanDu1,2*, ZicaiLiang1* 1Institute of Molecular Medicine, Peking University, Beijing, China, 2The State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, PekingUniversity,Beijing,China Abstract Ithasbeennotedthattargetsiteslocatedinthecodingregionorthe39-untranslatedregion(39-UTR)canbesilencedto significantlydifferentlevelsbythesamesiRNA,butlittleisknownaboutatwhatspecificitythesilencingwasachieved.Inan explorationofpositionaleffectsonsiRNAspecificitybyluciferasereportersystem,wesurprisinglydiscoveredthatsiRNA had greatly elevated tolerance towards mismatches in target sites in the 39-UTR of the mRNA compared with the same targetsitesclonedinthecodingregion.AssessmentofchangesinproteinandmRNAlevelssuggestedthatthedifferential mismatchtolerancemighthaveresultedfromlocation-specifictranslationalrepressioninthe39-UTR.Ablationofargonaute proteinsbyAGO-specificsiRNAsrevealedthattheAGO2hadmajorimpactonsiRNAsilencingactivityagainstsitesinboth codingregionand39-UTR,whilethesilencingofnonnucleolyticAGOproteins(AGO1,AGO3andAGO4)didnotsignificantly affectsilencingofsitesineitherregion.ThispaperrevealedthediscoverythatthespecificityofansiRNAcanbeaffectedby thelocationofitstargetsite. Citation: Wei N, Zhang L, Huang H, Chen Y, Zheng J, et al. (2012) siRNA Has Greatly Elevated Mismatch Tolerance at 39-UTR Sites. PLoS ONE 7(11): e49309. doi:10.1371/journal.pone.0049309 Editor:AlfredLewin,UniversityofFlorida,UnitedStatesofAmerica ReceivedJuly4,2012;AcceptedOctober8,2012;PublishedNovember8,2012 Copyright:?2012Weietal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermitsunrestricted use,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:ThisworkwassupportedbytheNationalNaturalScienceFoundationofChinanBeijingNaturalScienceF