RNA Chemical Modifications in Mammalian Skeletal Muscle Development, Homeostasis, and Disease: Regulatory Mechanisms and Chemical Biology Perspectives

Skeletal muscle is a core component of the motor system, responsible for movement, posture maintenance, and energy metabolism. It plays a vital role in physiological stress, injury repair, and metabolic homeostasis. In recent years, with the advancement of epigenetic research, RNA modification has become a hot topic in skeletal muscle biology. This article systematically reviews the progress in the study of RNA modification in regulating the fate of skeletal muscle, focusing on the dynamic regulatory mechanisms and pathophysiological significance of N6-methyladenosine (m6A) modification in muscle differentiation, regeneration, and atrophy. It also briefly introduces the existing evidence for 5-methylcytidine (m5C), adenosine-to-inosine (A-to-I) editing, and pseudouridine (Ψ) in skeletal muscle. A comprehensive understanding of these mechanisms is crucial for elucidating the physiological regulation of skeletal muscle and the pathogenesis of related diseases and also provides a new direction for the development of intervention strategies.