METTL21C mediates the occurrence of autophagy and formation of slow-twitch muscle fibers after exercise.

Homeostasis is essential for muscle repair and regeneration after skeletal muscle exercise. This study investigated the role of methyltransferase-like 21C (METTL21C) in skeletal muscle of mice after exercise and the potential mechanism. First, muscle samples were collected at 2, 4, and 6 weeks after exercise, liver glycogen, muscle glycogen, blood lactic acid (BLA) and triglyceride (TG) were assessed. Moreover, the expression levels of autophagy markers and METTL21C in skeletal muscle were analyzed. The results showed that the expressions of METTL21C and MYH7 in the gastrocnemius muscle of mice in the exercise group were significantly higher than that in the control group after exercise, which suggested that long-term exercise promoted the formation of slow-twitch muscle fibers in mouse skeletal muscle. Likewise, the autophagy capacity is enhanced with the extension of exercise in muscles. The findings were further verified in mouse C2C12 cells. We discovered that knockdown of Mettl21c reduced the expression of MYH7 and autophagy level in mouse myoblasts. These findings indicate that METTL21C promotes skeletal muscle homeostasis after exercise by enhancing autophagy, while METTL21C also contributes to differentiation of myogenic and formation of slow muscle fiber.