In:
PLOS Genetics, Public Library of Science (PLoS), Vol. 19, No. 9 ( 2023-9-7), p. e1010923-
Abstract:
Circular RNAs (circRNAs) have been recognized as critical regulators of skeletal muscle development. Myocyte enhancer factor 2A (MEF2A) is an evolutionarily conserved transcriptional factor that regulates myogenesis. However, it remains unclear whether MEF2A produces functional circRNAs. In this study, we identified two evolutionarily conserved circular MEF2A RNAs (circMEF2As), namely circMEF2A1 and circMEF2A2, in chicken and mouse muscle stem cells. Our findings revealed that circMEF2A1 promotes myogenesis by regulating the miR-30a-3p/PPP3CA/NFATC1 axis, whereas circMEF2A2 facilitates myogenic differentiation by targeting the miR-148a-5p/SLIT3/ROBO2/β-catenin signaling pathway. Furthermore, in vivo experiments demonstrated that circMEF2As both promote skeletal muscle growth. We also discovered that the linear MEF2A mRNA-derived MEF2A protein binds to its own promoter region, accelerating the transcription of MEF2A and upregulating the expression of both linear MEF2A and circMEF2As, forming a MEF2A autoregulated positive feedback loop. Moreover, circMEF2As positively regulate the expression of linear MEF2A by adsorbing miR-30a-3p and miR-148a-5p, which directly contribute to the MEF2A autoregulated feedback loop. Importantly, we found that mouse circMEF2As are essential for the myogenic differentiation of C2C12 cells. Collectively, our results demonstrated the evolution, function, and underlying mechanisms of circMEF2As in animal myogenesis, which may provide novel insight for both the farm animal meat industry and human medicine.
Type of Medium:
Online Resource
ISSN:
1553-7404
DOI:
10.1371/journal.pgen.1010923
DOI:
10.1371/journal.pgen.1010923.g001
DOI:
10.1371/journal.pgen.1010923.g002
DOI:
10.1371/journal.pgen.1010923.g003
DOI:
10.1371/journal.pgen.1010923.g004
DOI:
10.1371/journal.pgen.1010923.g005
DOI:
10.1371/journal.pgen.1010923.g006
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10.1371/journal.pgen.1010923.g007
DOI:
10.1371/journal.pgen.1010923.g008
DOI:
10.1371/journal.pgen.1010923.g009
DOI:
10.1371/journal.pgen.1010923.g010
DOI:
10.1371/journal.pgen.1010923.s001
DOI:
10.1371/journal.pgen.1010923.s002
DOI:
10.1371/journal.pgen.1010923.s003
DOI:
10.1371/journal.pgen.1010923.s004
DOI:
10.1371/journal.pgen.1010923.s005
DOI:
10.1371/journal.pgen.1010923.s006
DOI:
10.1371/journal.pgen.1010923.s007
DOI:
10.1371/journal.pgen.1010923.s008
DOI:
10.1371/journal.pgen.1010923.s009
DOI:
10.1371/journal.pgen.1010923.s010
DOI:
10.1371/journal.pgen.1010923.s011
DOI:
10.1371/journal.pgen.1010923.s012
DOI:
10.1371/journal.pgen.1010923.s013
DOI:
10.1371/journal.pgen.1010923.s014
DOI:
10.1371/journal.pgen.1010923.s015
DOI:
10.1371/journal.pgen.1010923.s016
DOI:
10.1371/journal.pgen.1010923.s017
DOI:
10.1371/journal.pgen.1010923.s018
DOI:
10.1371/journal.pgen.1010923.s019
DOI:
10.1371/journal.pgen.1010923.s020
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2186725-2
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