YTHDC1-Mediated m⁶A Modification of MAGI3 mRNA Regulates Proliferation and Differentiation of Myoblasts

The growth and maturation of skeletal muscle have a significant influence on the meat quality and quantity. N6-methyladenosine (m⁶A) is a dynamic and reversible modification that predominantly affects RNA stability, splicing, translation, nuclear export, and so on. M⁶A has been reported to be involved in the regulation of myogenesis. However, the mechanisms determining m⁶A modification in ovine skeletal muscle growth and development are still not well understood. We revealed the landscape of m⁶A modification in the skeletal muscle of the 70 day-old embryos (F70) and 40 day-old lambs (D40) using m⁶A-MeRIP-seq. In addition, we found that the m⁶A modification level of the membrane-associated guanylate kinase, WW, and PDZ domain containing 3 (MAGI3) gene significantly changed during skeletal muscle development. Further experimental verification showed that MAGI3 facilitated the proliferation and differentiation of ovine skeletal muscle satellite cells and C2C12 in vitro. Notably, YTHDC1 acts as an m⁶A reader to promote the degradation of the MAGI3 mRNA, thereby regulating myogenesis. These findings provide a comprehensive transcriptome profile of m⁶A methylation in ovine muscle at two key developmental stages. Additionally, MAGI3 modulated myogenesis in an m⁶A-YTHDC1-dependent manner.