Translational Control of the Myogenic Program in Developing, Regenerating, and Diseased Skeletal Muscle

Translational control of genes that code for protein allows a cell to rapidly respond to changes in its environment, in part because translational control of gene expression does not depend on upstream events required to produce an mRNA molecule. The importance of translational control has been highlighted by studies concerning muscle development, regeneration, and disease. Translational control of specific mRNAs is achieved by microRNAs and RNA-binding proteins, which are particularly relevant to developmental myogenesis, where they ensure the stepwise differentiation of multipotent progenitors to committed myogenic progenitors that ultimately fuse into slow- or fast-type myofibers that make up skeletal muscle. The importance of translational control is also illustrated in muscle disease, where deregulated microRNA expression accelerates or delays progression of disease. Skeletal muscle is also unique for its remarkable capacity to regenerate after injury, which requires the activity of quiescent muscle stem cells, named satellite cells for their position underneath the basal lamina of the myofiber. Mitotically quiescent satellite cells are primed to activate the cell cycle and myogenic program, a unique feature that requires specific regulation of mRNA translation converging with pathways that regulate global protein synthesis. Emerging concepts in translational control of gene expression have shed light on multiple layers of control over the myogenic program. In parallel, the development and regeneration of skeletal muscle represents a unique, relevant, and highly defined context within which new concepts in translational control of gene expression should emerge.