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

Hiroyuki Hirai, Mayank Verma, Shuichi Watanabe, Christopher Tastad, Yoko Asakura, Atsushi Asakura

Research output: Contribution to journalArticlepeer-review

122 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)347-365
Number of pages19
JournalJournal of Cell Biology
Volume191
Issue number2
DOIs
StatePublished - Oct 18 2010

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