Myogenin promoter-associated lncRNA Myoparr is essential for myogenic differentiation

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Article numbere47468
JournalEMBO Reports
Volume20
Issue number3
DOIs
Publication statusPublished - 01-03-2019

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Long Noncoding RNA
Myogenin
Muscle
Myoblasts
Skeletal Muscle
Histone Acetyltransferases
Muscular Atrophy
Muscle Development
Denervation
Muscular Diseases
MicroRNAs
Genetic Promoter Regions
Genes
Atrophy
Cell Cycle
Transcription Factors
Gene Expression
Muscles
Cells
Specifications

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

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title = "Myogenin promoter-associated lncRNA Myoparr is essential for myogenic differentiation",
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.",
author = "Keisuke Hitachi and Masashi Nakatani and Akihiko Takasaki and Yuya Ouchi and Akiyoshi Uezumi and Hiroshi Ageta and Hidehito Inagaki and Hiroki Kurahashi and Kunihiro Tsuchida",
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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, Vol. 20, No. 3, e47468, 01.03.2019.

Research output: Contribution to journalArticle

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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 - 2019/3/1

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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.

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