Mef2-mediated transcription of the miR379-410 cluster regulates activity-dependent dendritogenesis by fine-tuning Pumilio2 protein levels

Roberto Fiore, Sharof Khudayberdiev, Mette Christensen, Gabriele Siegel, Steven W. Flavell, Tae Kyung Kim, Michael E. Greenberg, Gerhard Schratt

Research output: Contribution to journalArticle

286 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)697-710
Number of pages14
JournalEMBO Journal
Volume28
Issue number6
DOIs
StatePublished - Mar 18 2009

Keywords

  • Dendritogenesis
  • Mef2
  • Neuronal activity
  • Pumilio
  • microRNA

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Fiore, R., Khudayberdiev, S., Christensen, M., Siegel, G., Flavell, S. W., Kim, T. K., Greenberg, M. E., & Schratt, G. (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. https://doi.org/10.1038/emboj.2009.10