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MyoD regulates apoptosis of myoblasts through microRNA-mediated down-regulation of Pax3

MyoD regulates apoptosis of myoblasts through microRNA-mediated down-regulation of Pax3 The molecules that regulate the apoptosis cascade are also involved in differentiation and syncytial fusion in skeletal muscle. MyoD is a myogenic transcription factor that plays essential roles in muscle differentiation. We noticed that MyoD −/− myoblasts display remarkable resistance to apoptosis by down-regulation of miR-1 (microRNA-1) and miR-206 and by up-regulation of Pax3. This resulted in transcriptional activation of antiapoptotic factors Bcl-2 and Bcl-xL. Forced MyoD expression induces up-regulation of miR-1 and miR-206 and down-regulation of Pax3, Bcl-2, and Bcl-xL along with increased apoptosis in MyoD −/− myoblasts. In contrast, MyoD gene knockdown increases cell survival of wild-type myoblasts. The 3′ untranslated region of Pax3 mRNA contains two conserved miR-1/miR-206–binding sites, which are required for targeting of these microRNAs (miRNAs). Therefore, these data suggest that MyoD not only regulates terminal differentiation but also apoptosis through miRNA-mediated down-regulation of Pax3. Finally, MyoD, miR-1, and miR-206 are all down-regulated in quiescent satellite cells, which may be required for maintenance of muscle stem cells. Footnotes Abbreviations used in this paper: APC allophycocyanin ASC activated satellite cell ChIP chromatin IP CMV cytomegalovirus CTX cardiotoxin Cyt c cytochrome c IP immunoprecipitation KD knockdown Luc luciferase MHC myosin heavy chain miRNA microRNA PE phycoerythrin QSC quiescent satellite cell shRNA short hairpin RNA UTR untranslated region Submitted: 3 June 2010 Accepted: 16 September 2010 This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms ). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/ ). http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Cell Biology Rockefeller University Press

MyoD regulates apoptosis of myoblasts through microRNA-mediated down-regulation of Pax3

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Publisher
Rockefeller University Press
Copyright
© 2010 Hirai et al.
ISSN
0021-9525
eISSN
1540-8140
DOI
10.1083/jcb.201006025
pmid
20956382
Publisher site
See Article on Publisher Site

Abstract

The molecules that regulate the apoptosis cascade are also involved in differentiation and syncytial fusion in skeletal muscle. MyoD is a myogenic transcription factor that plays essential roles in muscle differentiation. We noticed that MyoD −/− myoblasts display remarkable resistance to apoptosis by down-regulation of miR-1 (microRNA-1) and miR-206 and by up-regulation of Pax3. This resulted in transcriptional activation of antiapoptotic factors Bcl-2 and Bcl-xL. Forced MyoD expression induces up-regulation of miR-1 and miR-206 and down-regulation of Pax3, Bcl-2, and Bcl-xL along with increased apoptosis in MyoD −/− myoblasts. In contrast, MyoD gene knockdown increases cell survival of wild-type myoblasts. The 3′ untranslated region of Pax3 mRNA contains two conserved miR-1/miR-206–binding sites, which are required for targeting of these microRNAs (miRNAs). Therefore, these data suggest that MyoD not only regulates terminal differentiation but also apoptosis through miRNA-mediated down-regulation of Pax3. Finally, MyoD, miR-1, and miR-206 are all down-regulated in quiescent satellite cells, which may be required for maintenance of muscle stem cells. Footnotes Abbreviations used in this paper: APC allophycocyanin ASC activated satellite cell ChIP chromatin IP CMV cytomegalovirus CTX cardiotoxin Cyt c cytochrome c IP immunoprecipitation KD knockdown Luc luciferase MHC myosin heavy chain miRNA microRNA PE phycoerythrin QSC quiescent satellite cell shRNA short hairpin RNA UTR untranslated region Submitted: 3 June 2010 Accepted: 16 September 2010 This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms ). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/ ).

Journal

The Journal of Cell Biology – Rockefeller University Press

Published: Oct 18, 2010

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