Non-coding RNAs in skeletal muscle regeneration

Abstract

Following injury, skeletal muscles can regenerate from muscle specific stem cells, called satellite cells. Quiescent in uninjured muscles, satellite cells become activated, proliferate and differentiate into myotubes. Muscle regeneration occurs following distinct main overlapping phases, including inflammation, regeneration and maturation of the regenerated myofibers. Each step of muscle regeneration is orchestrated through complex signaling networks and gene regulatory networks, leading to the expression of specific set of genes in each concerned cell type. Apart from the well-established transcriptional mechanisms involving the myogenic regulatory factors of the MyoD family, increasing data indicate that each step of muscle regeneration is controlled by a wide range of non-coding RNAs. In this review, we discuss the role of two classes of non-coding RNAs (microRNAs and long non-coding RNAs) in the inflammatory, regeneration and maturation steps of muscle regeneration.

Keywords: Differentiation; Muscle regeneration; MyoD; Satellite cells; lncRNA; miRNA.

Fig. 1

Role of ncRNAs in the early differentiation of satellite cells. Upon muscle injury, Pax7 positive satellite cells are activated and differentiate into MyoD positive myogenic cells. Several non-coding RNAs have been described in the literature as regulating Pax7, Pax3 or MyoD expression in the early differentiation process of satellite cells.

Fig. 2

Control of the proliferative step of myoblasts by non-coding RNAs. During muscle regeneration, MyoD positive cells proliferate before differentiating into myotubes. This proliferative step is regulated by many non-coding RNAs targeting key cell cycle proteins and repressing the myogenic differentiation gene program.

Fig. 3

Role of ncRNAs in skeletal muscle differentiation. The committed myoblasts exit cell cycle to elongate and fuse into myotubes. Cell cycle withdrawal and myogenic differentiation are orchestrated by a network of non-coding RNAs controlling the muscle specific transcription factors, MyoD and myogenin, and different signaling pathways promoting myogenic differentiation.