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 (m(6)A) is a dynamic and reversible modification that predominantly affects RNA stability, splicing, translation, nuclear export, and so on. M(6)A has been reported to be involved in the regulation of myogenesis. However, the mechanisms determining m(6)A modification in ovine skeletal muscle growth and development are still not well understood. We revealed the landscape of m(6)A modification in the skeletal muscle of the 70 day-old embryos (F70) and 40 day-old lambs (D40) using m(6)A-MeRIP-seq. In addition, we found that the m(6)A 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 m(6)A reader to promote the degradation of the MAGI3 mRNA, thereby regulating myogenesis. These findings provide a comprehensive transcriptome profile of m(6)A methylation in ovine muscle at two key developmental stages. Additionally, MAGI3 modulated myogenesis in an m(6)A-YTHDC1-dependent manner.