MCPIP1 Down-Regulates IL-2 Expression through an ARE-Independent Pathway 英文参考文献.docVIP

MCPIP1 Down-Regulates IL-2 Expression through an ARE-Independent Pathway 英文参考文献.doc

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MCPIP1 Down-Regulates IL-2 Expression through an ARE-Independent Pathway 英文参考文献

MCPIP1Down-RegulatesIL-2ExpressionthroughanARE- IndependentPathway MinLi1.,WenqiangCao1.,HaifengLiu2,WeiZhang1,XiaLiu1,ZhijianCai1,JingGuo1,XuelianWang1, ZhaoyuanHui1,HangZhang1,JianliWang1*,LieWang1* 1InstituteofImmunology,ZhejiangUniversitySchoolofMedicine,Hangzhou,China,2LaboratoryofMolecularCellBiology,InstituteofBiochemistryandCellBiology, ChineseAcademyofSciences,Shanghai,China Abstract IL-2playsakeyroleinthesurvivalandproliferationofimmunecells,especiallyTlymphocytes.Itsexpressionisprecisely regulatedattranscriptionalandposttranscriptionallevel.IL-2isknowntoberegulatedbyRNAbindingproteins,suchas tristetraprolin(TTP),viaanAU-richelement(ARE)inthe39-untranslatedregion(39UTR)toinfluencethestabilityofmRNA. MCPIP1, identified as a novel RNase, can degrade IL-6, IL-12 and TNF-a mRNA by an ARE-independent pathway in the activationofmacrophages.Here,wereportedthatMCPIP1wasinducedintheactivationofTlymphocytesandnegatively regulatedIL-2geneexpressioninbothmouseandhumanprimaryTlymphocytesthroughdestabilizingitsmRNA.Asetof Luciferase reporter assay demonstrated that a non-ARE conserved element in IL-2 39UTR, which formed a stem-loop structure,respondedtoMCPIP1activity.RNAimmunoprecipitationandBiotinpulldownexperimentsfurthersuggestedthat MCPIP1couldmodestlybindtoIL-2mRNA.Takentogether,thesedatademonstratethatMCPIP1down-regulatesIL-2viaan ARE-independentpathway. Citation: Li M, Cao W, Liu H, Zhang W, Liu X, et al. (2012) MCPIP1 Down-Regulates IL-2 Expression through an ARE-Independent Pathway. PLoS ONE 7(11): e49841.doi:10.1371/journal.pone.0049841 Editor:GeorgStoecklin,GermanCancerResearchCenter,Germany ReceivedApril22,2012;AcceptedOctober12,2012;PublishedNovember21,2012 Copyright:?2012Lietal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermitsunrestricted use,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:ThisworkwassupportedbygrantsfromtheNationalNaturalScienceFoundationo

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