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Mef2-mediated transcription of the miR379–410 cluster regulates activity-dependent dendritogenesis by fine-tuning Pumilio2 protein levels
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...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2647767/ https://www.ncbi.nlm.nih.gov/pubmed/19197241 http://dx.doi.org/10.1038/emboj.2009.10 |
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author | Fiore, Roberto Khudayberdiev, Sharof Christensen, Mette Siegel, Gabriele Flavell, Steven W Kim, Tae-Kyung Greenberg, Michael E Schratt, Gerhard |
author_facet | Fiore, Roberto Khudayberdiev, Sharof Christensen, Mette Siegel, Gabriele Flavell, Steven W Kim, Tae-Kyung Greenberg, Michael E Schratt, Gerhard |
author_sort | Fiore, Roberto |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-2647767 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-26477672009-02-25 Mef2-mediated transcription of the miR379–410 cluster regulates activity-dependent dendritogenesis by fine-tuning Pumilio2 protein levels Fiore, Roberto Khudayberdiev, Sharof Christensen, Mette Siegel, Gabriele Flavell, Steven W Kim, Tae-Kyung Greenberg, Michael E Schratt, Gerhard EMBO J Article 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. Nature Publishing Group 2009-03-18 2009-02-05 /pmc/articles/PMC2647767/ /pubmed/19197241 http://dx.doi.org/10.1038/emboj.2009.10 Text en Copyright © 2009, European Molecular Biology Organization http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This licence does not permit commercial exploitation without specific permission. |
spellingShingle | Article Fiore, Roberto Khudayberdiev, Sharof Christensen, Mette Siegel, Gabriele Flavell, Steven W Kim, Tae-Kyung Greenberg, Michael E Schratt, Gerhard Mef2-mediated transcription of the miR379–410 cluster regulates activity-dependent dendritogenesis by fine-tuning Pumilio2 protein levels |
title | Mef2-mediated transcription of the miR379–410 cluster regulates activity-dependent dendritogenesis by fine-tuning Pumilio2 protein levels |
title_full | Mef2-mediated transcription of the miR379–410 cluster regulates activity-dependent dendritogenesis by fine-tuning Pumilio2 protein levels |
title_fullStr | Mef2-mediated transcription of the miR379–410 cluster regulates activity-dependent dendritogenesis by fine-tuning Pumilio2 protein levels |
title_full_unstemmed | Mef2-mediated transcription of the miR379–410 cluster regulates activity-dependent dendritogenesis by fine-tuning Pumilio2 protein levels |
title_short | Mef2-mediated transcription of the miR379–410 cluster regulates activity-dependent dendritogenesis by fine-tuning Pumilio2 protein levels |
title_sort | mef2-mediated transcription of the mir379–410 cluster regulates activity-dependent dendritogenesis by fine-tuning pumilio2 protein levels |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2647767/ https://www.ncbi.nlm.nih.gov/pubmed/19197241 http://dx.doi.org/10.1038/emboj.2009.10 |
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