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<p>The regulatory role of N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) modification in skeletal muscle myogenesis and muscle homeostasis remains poorly characterized, particularly regarding the functional significance of methyltransferase-like 3 (METTL3), the catalytic subunit of the m<sup>6</sup>A methyltransferase complex (MTC), in myogenic regulation. Through systematic investigation of m<sup>6</sup>A epitranscriptomic remodeling during myogenesis, we demonstrate that METTL3-mediated m<sup>6</sup>As orchestrates myoblast fusion processes in both differentiation and regeneration contexts. Notably, we observed marked induction of <i>Mettl3</i> expression post-injury, accompanied by substantial transcriptomic alterations in myogenesis-related pathways. High-resolution m<sup>6</sup>A mapping revealed distinct dynamic patterns of METTL3-regulated m<sup>6</sup>As during differentiation, exhibiting dichotomous regulation across target transcripts. Mechanistically, we identified myogenic fusion factors <i>Mymx</i> and <i>Mymk</i> as direct targets of METTL3, showing concomitant upregulation of both transcript abundance and m<sup>6</sup>A deposition during myogenesis. This study provides comprehensive multi-omics resources delineating the mechanistic landscape of METTL3-regulated m<sup>6</sup>As in myogenic programming, establishing METTL3 as a critical regulatory node governing myoblast fusion dynamic.</p>

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Stage-specific requirement for METTL3-dependent m6A epitranscriptomic regulation during myogenesis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月30日

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  • Ye-Ya Tan,
  • Yang-Wen Ou,
  • Qin Zuo,
  • Yi Luo,
  • Wei-Cai Chen,
  • Wan-Xin Chen,
  • Xin-Wang Zhi,
  • Pei-Wen Lin,
  • Jia-Xing Lu,
  • Peng Liu,
  • Si-Min Liang,
  • Qing-Hai Lian,
  • Lian-Dong Zuo,
  • Hong-Wen Xu,
  • Shu-Juan Xie

摘要

The regulatory role of N6-methyladenosine (m6A) modification in skeletal muscle myogenesis and muscle homeostasis remains poorly characterized, particularly regarding the functional significance of methyltransferase-like 3 (METTL3), the catalytic subunit of the m6A methyltransferase complex (MTC), in myogenic regulation. Through systematic investigation of m6A epitranscriptomic remodeling during myogenesis, we demonstrate that METTL3-mediated m6As orchestrates myoblast fusion processes in both differentiation and regeneration contexts. Notably, we observed marked induction of Mettl3 expression post-injury, accompanied by substantial transcriptomic alterations in myogenesis-related pathways. High-resolution m6A mapping revealed distinct dynamic patterns of METTL3-regulated m6As during differentiation, exhibiting dichotomous regulation across target transcripts. Mechanistically, we identified myogenic fusion factors Mymx and Mymk as direct targets of METTL3, showing concomitant upregulation of both transcript abundance and m6A deposition during myogenesis. This study provides comprehensive multi-omics resources delineating the mechanistic landscape of METTL3-regulated m6As in myogenic programming, establishing METTL3 as a critical regulatory node governing myoblast fusion dynamic.