Gene Network and Pathway Analysis of Mice with Conditional Ablation of Dicer in Post-Mitotic Neurons 英文参考文献.docVIP

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Gene Network and Pathway Analysis of Mice with Conditional Ablation of Dicer in Post-Mitotic Neurons 英文参考文献.doc

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Gene Network and Pathway Analysis of Mice with Conditional Ablation of Dicer in Post-Mitotic Neurons 英文参考文献

GeneNetworkandPathwayAnalysisofMicewith ConditionalAblationofDicerinPost-MitoticNeurons Ve′roniqueDorval1,2,PascalY.Smith1,2,CharlotteDelay1,2,EzequielCalvo1,2,EmmanuelPlanel1,2 Nade`geZommer3,4,LucBue′e3,4,Se′bastienS.He′bert1,2 , * 1Axe Neurosciences, Centre de Recherche du CHUQ (CHUL), Que′bec, Que′bec, Canada, 2De′partement de Psychiatrie et de Neurosciences, Universite′ Laval, Que′bec, Que′bec,Canada,3Universite′ Lille-NorddeFrance,UDSL,Faculte′ deMe′decine,Lille,France,4Inserm,UMR837,Lille,France Abstract Background: The small non-protein-coding microRNAs (miRNAs) have emerged as critical regulators of neuronal differentiation,identityandsurvival.Todate,however,littleisknownaboutthegenesandmolecularnetworksregulatedby neuronalmiRNAsinvivo,particularlyintheadultmammalianbrain. Methodology/PrincipalFindings:WeanalyzedwholegenomemicroarraysfrommicelackingDicer,theenzymeresponsible for miRNA production, specifically in postnatal forebrain neurons. A total of 755 mRNA transcripts were significantly (P,0.05,FDR,0.25)misregulatedintheconditionalDicerknockoutmice.Tengenes,includingTnrc6c,Dnmt3a,andLimk1, were validated by real time quantitative RT-PCR. Upregulated transcripts were enriched in nonneuronal genes, which is consistentwithpreviousstudiesinvitro.Microarraydataminingshowedthatupregulatedgeneswereenrichedinbiological processes related to gene expression regulation, while downregulated genes were associated with neuronal functions. Molecularpathwaysassociatedwithneurologicaldisorders,cellularorganizationandcellularmaintenancewerealteredin theDicermutantmice.NumerousmiRNAtargetsiteswereenrichedinthe39untranslatedregion(39UTR)ofupregulated genes,themostsignificantcorrespondingtothemiR-124seedsequence.Interestingly,ourresultssuggestthat,inaddition tomiR-124,alargefractionoftheneuronalmiRNomeparticipates,byorderofabundance,incoordinatedgeneexpression regulationandneuronalmaintenance. Conclusions/Significance:Takentogether,theseresultsprovidenewcluesintothero