1. Myogenin promoter‐associated lnc <scp>RNA</scp> Myoparr is essential for myogenic differentiation
- Author
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Akiyoshi Uezumi, Yuya Ouchi, Masashi Nakatani, Akihiko Takasaki, Keisuke Hitachi, Hiroki Kurahashi, Kunihiro Tsuchida, Hidehito Inagaki, and Hiroshi Ageta
- Subjects
0303 health sciences ,Myogenesis ,Skeletal muscle ,Articles ,Biology ,Muscle disorder ,MyoD ,Biochemistry ,Cell biology ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,microRNA ,Genetics ,Transcriptional regulation ,medicine ,Myocyte ,Molecular Biology ,030217 neurology & neurosurgery ,Myogenin ,030304 developmental biology - Abstract
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.
- Published
- 2019