MicroRNA-277 Modulates the Neurodegeneration Caused by Fragile X Premutation rCGG Repeats 英文参考文献.docVIP

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MicroRNA-277 Modulates the Neurodegeneration Caused by Fragile X Premutation rCGG Repeats 英文参考文献.doc

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MicroRNA-277 Modulates the Neurodegeneration Caused by Fragile X Premutation rCGG Repeats 英文参考文献

MicroRNA-277ModulatestheNeurodegeneration CausedbyFragileXPremutationrCGGRepeats HuipingTan1,2,MickaelPoidevin1,HeLi2,DahuaChen3*,PengJin1* 1Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, United States of America, 2Division of Histology and Embryology, Tongji MedicalCollege,HuazhongUniversityofScienceandTechnology,Wuhan,China,3StateKeyLaboratoryofReproductiveBiology,InstituteofZoology,ChineseAcademy ofSciences,Beijing,China Abstract Fragile X-associated tremor/ataxia syndrome (FXTAS), a late-onset neurodegenerative disorder, has been recognized in oldermalefragileXpremutationcarriersandisuncoupledfromfragileXsyndrome.UsingaDrosophilamodelofFXTAS,we previously showed that transcribed premutation repeats alone are sufficient to cause neurodegeneration. MiRNAs are sequence-specific regulators of post-transcriptional gene expression. To determine the role of miRNAs in rCGG repeat- mediatedneurodegeneration,weprofiledmiRNAexpressionandidentifiedselectivemiRNAs,includingmiR-277,thatare alteredspecificallyinDrosophilabrainsexpressingrCGGrepeats.WetestedtheirgeneticinteractionswithrCGGrepeatsand foundthatmiR-277canmodulaterCGGrepeat-mediatedneurodegeneration.Furthermore,weidentifiedDrep-2andVimar as functional targets of miR-277 that could modulate rCGG repeat-mediated neurodegeneration. Finally, we found that hnRNPA2/B1,anrCGGrepeat-bindingprotein,candirectlyregulatetheexpressionofmiR-277.Theseresultssuggestthat sequestrationofspecificrCGGrepeat-bindingproteinscouldleadtoaberrantexpressionofselectivemiRNAs,whichmay modulate the pathogenesis of FXTAS by post-transcriptionally regulating the expression of specific mRNAs involved in FXTAS. Citation:TanH,PoidevinM,LiH,ChenD,JinP(2012)MicroRNA-277ModulatestheNeurodegenerationCausedbyFragileXPremutationrCGGRepeats.PLoS Genet8(5):e1002681.doi:10.1371/journal.pgen.1002681 Editor:HarryT.Orr,UniversityofMinnesota,UnitedStatesofAmerica ReceivedNovember16,2011;AcceptedMarch15,2012;PublishedMay3,