Mef2-Mediated Transcription of the miR379–410 Cluster Regulates Activity-Dependent Dendritogenesis by Fine-Tuning Pumilio2 Protein Levels

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Mef2-Mediated Transcription of the miR379–410 Cluster Regulates Activity-Dependent Dendritogenesis by Fine-Tuning Pumilio2 Protein Levels

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dc.contributor.author Fiore, Roberto
dc.contributor.author Khudayberdiev, Sharof
dc.contributor.author Christensen, Mette
dc.contributor.author Siegel, Gabriele
dc.contributor.author Flavell, Steven W
dc.contributor.author Schratt, Gerhard
dc.contributor.author Kim, Tae-Kyung
dc.contributor.author Greenberg, Michael Eldon
dc.date.accessioned 2011-04-26T16:44:42Z
dc.date.issued 2009
dc.identifier.citation Fiore, Roberto, Sharof Khudayberdiev, Mette Christensen, Gabriele Siegel, Steven W. Flavell, Tae-Kyung Kim, Michael E. Greenberg, and Gerhard Schratt. 2009. Mef2-mediated transcription of the miR379–410 cluster regulates activity-dependent dendritogenesis by fine-tuning Pumilio2 protein levels. EMBO Journal 28(6): 697-710. en_US
dc.identifier.issn 0261-4189 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:4876369
dc.description.abstract Neuronal activity orchestrates the proper development of the neuronal circuitry by regulating both transcriptional and post-transcriptional gene expression programmes. How these programmes are coordinated, however, is largely unknown. We found that the transcription of miR379–410, a large cluster of brain-specific microRNAs (miRNAs), is induced by increasing neuronal activity in primary rat neurons. Results from chromatin immunoprecipitation and luciferase reporter assays suggest that binding of the transcription factor myocyte enhancing factor 2 (Mef2) upstream of miR379–410 is necessary and sufficient for activity-dependent transcription of the cluster. Mef2-induced expression of at least three individual miRNAs of the miR379–410 cluster is required for activity-dependent dendritic outgrowth of hippocampal neurons. One of these miRNAs, the dendritic miR-134, promotes outgrowth by inhibiting translation of the mRNA encoding for the translational repressor Pumilio2. In summary, we have described a novel regulatory pathway that couples activity-dependent transcription to miRNA-dependent translational control of gene expression during neuronal development. en_US
dc.language.iso en_US en_US
dc.publisher Nature Publishing Group en_US
dc.relation.isversionof doi:10.1038/emboj.2009.10 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2647767/pdf/ en_US
dash.license LAA
dc.subject dendritogenesis en_US
dc.subject Mef2 en_US
dc.subject microRNA en_US
dc.subject neuronal activity en_US
dc.subject Pumilio en_US
dc.title Mef2-Mediated Transcription of the miR379–410 Cluster Regulates Activity-Dependent Dendritogenesis by Fine-Tuning Pumilio2 Protein Levels en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal EMBO Journal en_US
dash.depositing.author Greenberg, Michael Eldon
dc.date.available 2011-04-26T16:44:42Z
dash.affiliation.other HMS^Microbiology and Molecular Genetics en_US
dash.affiliation.other HMS^Neurology-Children's Hospital en_US
dash.affiliation.other HMS^Neurobiology en_US

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