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Long noncoding RNA SYISL regulates myogenesis by interacting with polycomb repressive complex 2.


ABSTRACT: Although many long noncoding RNAs (lncRNAs) have been identified in muscle, their physiological function and regulatory mechanisms remain largely unexplored. In this study, we systematically characterized the expression profiles of lncRNAs during C2C12 myoblast differentiation and identified an intronic lncRNA, SYISL (SYNPO2 intron sense-overlapping lncRNA), that is highly expressed in muscle. Functionally, SYISL promotes myoblast proliferation and fusion but inhibits myogenic differentiation. SYISL knockout in mice results in significantly increased muscle fiber density and muscle mass. Mechanistically, SYISL recruits the enhancer of zeste homolog 2 (EZH2) protein, the core component of polycomb repressive complex 2 (PRC2), to the promoters of the cell-cycle inhibitor gene p21 and muscle-specific genes such as myogenin (MyoG), muscle creatine kinase (MCK), and myosin heavy chain 4 (Myh4), leading to H3K27 trimethylation and epigenetic silencing of target genes. Taken together, our results reveal that SYISL is a repressor of muscle development and plays a vital role in PRC2-mediated myogenesis.

SUBMITTER: Jin JJ 

PROVIDER: S-EPMC6196504 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Long noncoding RNA <i>SYISL</i> regulates myogenesis by interacting with polycomb repressive complex 2.

Jin Jian Jun JJ   Lv Wei W   Xia Pan P   Xu Zai Yan ZY   Zheng An Dai AD   Wang Xiao Jing XJ   Wang Shan Shan SS   Zeng Rui R   Luo Hong Mei HM   Li Guo Liang GL   Zuo Bo B  

Proceedings of the National Academy of Sciences of the United States of America 20181002 42


Although many long noncoding RNAs (lncRNAs) have been identified in muscle, their physiological function and regulatory mechanisms remain largely unexplored. In this study, we systematically characterized the expression profiles of lncRNAs during C2C12 myoblast differentiation and identified an intronic lncRNA, <i>SYISL</i> (<i>SYNPO2</i> intron sense-overlapping lncRNA), that is highly expressed in muscle. Functionally, <i>SYISL</i> promotes myoblast proliferation and fusion but inhibits myogen  ...[more]

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