TY - JOUR
T1 - Myogenin promoter-associated lncRNA Myoparr is essential for myogenic differentiation
AU - Hitachi, Keisuke
AU - Nakatani, Masashi
AU - Takasaki, Akihiko
AU - Ouchi, Yuya
AU - Uezumi, Akiyoshi
AU - Ageta, Hiroshi
AU - Inagaki, Hidehito
AU - Kurahashi, Hiroki
AU - Tsuchida, Kunihiro
N1 - Funding Information:
We thank Dr. H. Danno for technical advice. This work was supported in part by JSPS KAKENHI (25860151, 16K08599, and 17K08646), Intramural Research Grants (26-8 and 29-4) for Neurological and Psychiatric Disorders of NCNP, and a Grant-in-Aid from the NAKATOMI Foundation.
Publisher Copyright:
© 2019 The Authors
PY - 2019/3
Y1 - 2019/3
N2 - 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.
AB - 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.
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U2 - 10.15252/embr.201847468
DO - 10.15252/embr.201847468
M3 - Article
C2 - 30622218
AN - SCOPUS:85059674791
VL - 20
JO - EMBO Reports
JF - EMBO Reports
SN - 1469-221X
IS - 3
M1 - e47468
ER -