RNAa Is Conserved in Mammalian Cells 英文参考文献.docVIP

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RNAa Is Conserved in Mammalian Cells 英文参考文献.doc

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RNAa Is Conserved in Mammalian Cells 英文参考文献

RNAaIsConservedinMammalianCells VeraHuang1,2,YiQin1,2,JiWang1,2,XiaolingWang1,2,RobertF.Place1,2,GuitingLin2,TomF.Lue2 ,Long- ChengLi1,2 * 1Helen-Diller Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, United States of America, 2Department of Urology, UniversityofCaliforniaSanFrancisco,SanFrancisco,California,UnitedStatesofAmerica Abstract Background: RNA activation (RNAa) is a newly discovered mechanism of gene activation triggered by small double- strandedRNAstermed‘smallactivatingRNAs’(saRNAs).Thusfar,RNAahasonlybeendemonstratedinhumancellsandis unclearwhetheritisconservedinothermammals. Methodology/PrincipalFindings:Inthepresentstudy,weevaluatedRNAaincellsderivedfromfourmammalianspecies includingnonhumanprimates(Africangreenmonkeyandchimpanzee),mouse,andrat.Previously,weidentifiedsaRNAs leadingtotheactivationofE-cadherin,p21,andVEGFinhumancells.Asthetargetedsequencesarehighlyconservedin primates,transfectionofeachhumansaRNAintoAfricangreenmonkey(COS1)andchimpanzee(WES)cellsalsoresultedin inductionoftheintendedgene.AdditionalsaRNAstargetingclinicallyrelevantgenesincludingp53,PAR4,WT1,RB1,p27, NKX3-1,VDR,IL2,andpS2werealsodesignedandtransfectedintoCOS1andWEScells.Oftheninegenes,p53,PAR4,WT1, andNKX3-1wereinducedbytheircorrespondingsaRNAs.WefurtherextendedouranalysisofRNAaintorodentcelltypes. WeidentifiedtwosaRNAsthatinducedtheexpressionofmouseCyclinB1inNIH/3T3andTRAMPC1cells,whichledto increasedphosphorylationofhistoneH3,adownstreammarkerforchromosomecondensationandentryintomitosis.We alsoidentifiedtwosaRNAsthatactivatedtheexpressionofCXCR4inprimaryratadipose–derivedstemcells. Conclusions/Significance:ThisstudydemonstratesthatRNAaexistsinmammalianspeciesotherthanhuman.Ourfindings alsosuggestthatnonhumanprimatediseasemodelsmayhaveclinicalapplicabilityforvalidatingRNAa-baseddrugs. Citation:HuangV,QinY,WangJ,WangX,PlaceRF,etal.(2010)RNAaIsConservedinMammalianCells.PLoSONE5(1):e8848.doi:10.1371/journal.pone.0008848 Edit