Expression and Rhythmic Modulation of Circulating MicroRNAs Targeting the Clock Gene Bmal1 in Mice 英文参考文献.docVIP
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Expression and Rhythmic Modulation of Circulating MicroRNAs Targeting the Clock Gene Bmal1 in Mice 英文参考文献
ExpressionandRhythmicModulationofCirculating
MicroRNAsTargetingtheClockGeneBmal1inMice
VikramR.Shende1,2,MariannaM.Goldrick4,SuchitraRamani4,DavidJ.Earnest1,2,3*
1DepartmentofBiology,TexasAMUniversity,CollegeStation,Texas,UnitedStatesofAmerica,2CenterforBiologicalClocksResearch,TexasAMUniversity,College
Station,Texas,UnitedStatesofAmerica,3DepartmentofNeuroscienceandExperimentalTherapeutics,CollegeofMedicine,TexasAMUniversityHealthScienceCenter,
CollegeStation,Texas,UnitedStatesofAmerica,4BIOOScientific,Austin,Texas,UnitedStatesofAmerica
Abstract
MicroRNAs (miRNAs) interact with 39 untranslated region (UTR) elements of target genes to regulate mRNA stability or
translation andthus play arole in regulating manydifferent biological processes,including circadian rhythms. However,
specific miRNAs mediating the regulation of essential clock genes remain largely unknown. Because vesicles containing
membrane-boundmiRNAsarepresentinthecirculatorysystem,weexaminedmiRNAspredictedtotargettheclockgene,
Bmal1,forevidenceofrhythmicfluctuationsincirculatinglevelsandmodulatoryeffectsonthe39UTRactivityofBmal1 .A
numberofmiRNAswithBmal1asapredictedtargetwereexpressedintheserumofmiceexposedtoLD12:12andofthese
miRNAs,miR-152andmiR-494butnotmiR-142-3pweremarkedbydiurnaloscillationswithbimodalpeaksinexpression
occurring near the middle of the day and 8 or 12hr later during the night. Co-transfection of pre-miR over-expression
constructsformiR-494andmiR-142-3pinHEK293cellshadsignificanteffectsinrepressingluciferase-reportedBmal139UTR
activity by asmuch as60%, suggesting that these miRNAsmay functionas post-transcriptional modulators of Bmal1 .In
conjunctionwithpreviousstudiesimplicatingmiRNAsasextracellularregulatorysignals,ourresultssuggestthatcirculating
miRNAsmayplayaroleintheregulationofthemolecularclockworksinperipheralcircadianoscillators.
Citation:ShendeVR,GoldrickMM,RamaniS,EarnestDJ(2011)ExpressionandRhythmicModulationofCirculatingMicroRNAsTargetingtheClockGeneBmal1in
Mice.PLoS
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