Ribosome dynamics during skeletal muscle repair and regeneration in mice and humans

Skeletal muscle repair requires coordinated regulation of inflammation and protein synthesis, but the roles of ribosome biogenesis and protein composition remain poorly defined. To address this, mice underwent femoral artery ligation (FAL) to induce muscle regeneration over 28 days. In humans, tibialis anterior biopsies from patients with traumatic tibial fracture were subjected to RNA sequencing. Following FAL, c-Myc mRNA increased transiently, followed by increased ribosomal DNA transcription, leading to elevated total RNA levels. Skeletal muscle-specific ribosomal protein paralog RPL3L was replaced by the ubiquitously expressed RPL3 during the initial phases of recovery, but this shift was reversed by day 28. A substantial transcriptomic response was observed in human muscle injury, with heavy emphasis on MYC-induced anabolism and inflammation. This supports a model in which MYC-driven changes in ribosomal content and composition form a core anabolic module in skeletal muscle repair, potentially representing a targetable axis to enhance recovery after muscle injury.NEW & NOTEWORTHY Our findings establish ribosome biogenesis and ribosome remodeling as core components of the skeletal muscle regenerative program conserved across species. The rapid, MYC-driven induction of translational capacity, coupled with a transient switch in ribosomal protein composition, increases ribosome heterogeneity during skeletal muscle regeneration.