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Evolutionary conserved circular MEF2A RNAs regulate myogenic differentiation and skeletal muscle development.
Xiaoxu Shen1,2, Xiyu Zhao1,2, Haorong He1,2
1Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, China.
Plos Genetics
|September 7, 2023
Summary
Two novel circular RNAs derived from MEF2A (circMEF2As) were discovered and shown to promote skeletal muscle growth and myogenic differentiation in animals. These circRNAs form a positive feedback loop with MEF2A, impacting muscle development.
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are key regulators of skeletal muscle development.
- Myocyte enhancer factor 2A (MEF2A) is a crucial transcription factor for myogenesis.
- The role of MEF2A-derived circRNAs in myogenesis is not well understood.
Purpose of the Study:
- To identify and characterize MEF2A-derived circRNAs (circMEF2As) in muscle stem cells.
- To elucidate the functions and regulatory mechanisms of circMEF2As in myogenesis.
- To investigate the interplay between linear MEF2A, circMEF2As, and myogenic regulatory pathways.
Main Methods:
- Identification of circRNAs in chicken and mouse muscle stem cells.
- Functional assays in C2C12 cells and in vivo skeletal muscle models.
- Analysis of miRNA-target interactions and gene expression.
- Investigation of transcriptional regulation and feedback loops.
Main Results:
- Two conserved circMEF2As (circMEF2A1 and circMEF2A2) were identified.
- circMEF2A1 promotes myogenesis via the miR-30a-3p/PPP3CA/NFATC1 pathway.
- circMEF2A2 facilitates myogenic differentiation through the miR-148a-5p/SLIT3/ROBO2/β-catenin pathway.
- circMEF2As enhance skeletal muscle growth in vivo.
- A positive feedback loop involving linear MEF2A, circMEF2As, and miRNAs was established.
- circMEF2As are essential for myogenic differentiation of C2C12 cells.
Conclusions:
- circMEF2As are evolutionarily conserved regulators of animal myogenesis.
- circMEF2As play distinct roles in promoting skeletal muscle development through specific molecular pathways.
- circMEF2As are integral components of an autoregulated MEF2A feedback loop.
- These findings offer insights into skeletal muscle biology relevant to animal agriculture and human medicine.
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