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.
| Language | English |
|---|---|
| Article number | e47468 |
| Journal | EMBO Reports |
| DOIs | |
| Publication status | Accepted/In press - 01-01-2019 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Biology
- Genetics
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Myogenin promoter-associated lncRNA Myoparr is essential for myogenic differentiation. / Hitachi, Keisuke; Nakatani, Masashi; Takasaki, Akihiko; Ouchi, Yuya; Uezumi, Akiyoshi; Ageta, Hiroshi; Inagaki, Hidehito; Kurahashi, Hiroki; Tsuchida, Kunihiro.
In: EMBO Reports, 01.01.2019.Research output: Contribution to journal › Article
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
PY - 2019/1/1
Y1 - 2019/1/1
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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UR - http://www.scopus.com/inward/citedby.url?scp=85059674791&partnerID=8YFLogxK
U2 - 10.15252/embr.201847468
DO - 10.15252/embr.201847468
M3 - Article
JO - EMBO Reports
T2 - EMBO Reports
JF - EMBO Reports
SN - 1469-221X
M1 - e47468
ER -