Premium
Mef2‐mediated transcription of the miR379–410 cluster regulates activity‐dependent dendritogenesis by fine‐tuning Pumilio2 protein levels
Author(s) -
Fiore Roberto,
Khudayberdiev Sharof,
Christensen Mette,
Siegel Gabriele,
Flavell Steven W,
Kim TaeKyung,
Greenberg Michael E,
Schratt Gerhard
Publication year - 2009
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2009.10
Subject(s) - biology , mef2 , transcription factor , chromatin immunoprecipitation , microrna , microbiology and biotechnology , transcription (linguistics) , repressor , regulation of gene expression , gene expression , gene , enhancer , genetics , promoter , linguistics , philosophy
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.