YTHDC1-Mediated m ⁶ A 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 (<i>MAGI3</i>) gene significantly changed during skeletal muscle development. Further experimental verification showed that <i>MAGI3</i> 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 <i>MAGI3</i> mRNA, thereby regulating myogenesis. These findings provide a comprehensive transcriptome profile of m⁶A methylation in ovine muscle at two key developmental stages. Additionally, <i>MAGI3</i> modulated myogenesis in an m⁶A-YTHDC1-dependent manner.