Myogenin promoter-associated lncRNA Myoparr is essential for myogenic differentiation

Keisuke Hitachi, Masashi Nakatani, Akihiko Takasaki, Yuya Ouchi, Akiyoshi Uezumi, Hiroshi Ageta, Hidehito Inagaki, Hiroki Kurahashi, Kunihiro Tsuchida

研究成果: Article

9 引用 (Scopus)

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Promoter-associated long non-coding RNAs (lncRNAs) regulate the expression of adjacent genes; however, precise roles of these lncRNAs in skeletal muscle remain largely unknown. Here, we characterize a promoter-associated lncRNA, Myoparr, in myogenic differentiation and muscle disorders. Myoparr is expressed from the promoter region of the mouse and human myogenin gene, one of the key myogenic transcription factors. We show that Myoparr is essential both for the specification of myoblasts by activating neighboring myogenin expression and for myoblast cell cycle withdrawal by activating myogenic microRNA expression. Mechanistically, Myoparr interacts with Ddx17, a transcriptional coactivator of MyoD, and regulates the association between Ddx17 and the histone acetyltransferase PCAF. Myoparr also promotes skeletal muscle atrophy caused by denervation, and knockdown of Myoparr rescues muscle wasting in mice. Our findings demonstrate that Myoparr is a novel key regulator of muscle development and suggest that Myoparr is a potential therapeutic target for neurogenic atrophy in humans.

元の言語English
記事番号e47468
ジャーナルEMBO Reports
20
発行部数3
DOI
出版物ステータスPublished - 03-2019

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Genetics

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