The requirement of Mettl3-promoted MyoD mRNA maintenance in proliferative myoblasts for skeletal muscle differentiation

Kensuke Kudou, Tetsuro Komatsu, Jumpei Nogami, Kazumitsu Maehara, Akihito Harada, Hiroshi Saeki, Eiji Oki, Yoshihiko Maehara, Yasuyuki Ohkawa

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Myogenic progenitor/stem cells retain their skeletal muscle differentiation potential by maintaining myogenic transcription factors such as MyoD. However, the mechanism of how MyoD expression is maintained in proliferative progenitor cells has not been elucidated. Here, we found that MyoD expression was reduced at the mRNA level by cell cycle arrest in S and G2 phases, which in turn led to the absence of skeletal muscle differentiation. The reduction of MyoD mRNA was correlated with the reduced expression of factors regulating RNA metabolism, including methyltransferase like 3 (Mettl3), which induces N6-methyladenosine (m6A) modifications of RNA. Knockdown of Mettl3 revealed that MyoD RNA was specifically downregulated and that this was caused by a decrease in processed, but not unprocessed, mRNA. Potential m6A modification sites were profiled by m6A sequencing and identified within the 50 untranslated region (UTR) of MyoD mRNA. Deletion of the 50 UTR revealed that it has a role in MyoD mRNA processing. These data showed that Mettl3 is required for MyoD mRNA expression in proliferative myoblasts.

Original languageEnglish
Article number170119
JournalOpen Biology
Volume7
Issue number9
DOIs
Publication statusPublished - Jan 1 2017

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Myoblasts
Methyltransferases
Muscle
Skeletal Muscle
Maintenance
Messenger RNA
Untranslated Regions
Stem Cells
RNA
G2 Phase
Cell Cycle Checkpoints
Stem cells
S Phase
Metabolism
Transcription Factors
Down-Regulation
Cells
Processing

All Science Journal Classification (ASJC) codes

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

Cite this

The requirement of Mettl3-promoted MyoD mRNA maintenance in proliferative myoblasts for skeletal muscle differentiation. / Kudou, Kensuke; Komatsu, Tetsuro; Nogami, Jumpei; Maehara, Kazumitsu; Harada, Akihito; Saeki, Hiroshi; Oki, Eiji; Maehara, Yoshihiko; Ohkawa, Yasuyuki.

In: Open Biology, Vol. 7, No. 9, 170119, 01.01.2017.

Research output: Contribution to journalArticle

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AU - Harada, Akihito

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