RPS27L Maintains Nucleolar Homeostasis to Regulate Proliferation and Differentiation of Bovine Skeletal Muscle Satellite Cells

The in vitro expansion of bovine skeletal muscle satellite cells (SMSCs) is critical for cultured meat production. Here, we investigated the role of ribosomal protein S27-like (RPS27L) in regulating satellite cell proliferation and differentiation. RPS27L knockdown markedly inhibited proliferation and promoted myogenic differentiation, whereas RPS27L overexpression exerted opposite effects. Interestingly, both RPS27L depletion and overexpression activated the p53 signaling pathway. Further analyses revealed that disruption of RPS27L homeostasis, regardless of direction, induced nucleolar stress. These findings suggest that proper RPS27L dosage is required to maintain nucleolar homeostasis and normal satellite cell function. Aberrant RPS27L expression activates the nucleolar stress-p53 axis and alters the balance between proliferation and differentiation in bovine skeletal muscle satellite cells. These findings reveal a non-canonical mechanism of p53 regulation in which disturbance of RPS27L homeostasis, rather than simple loss of RPS27L function, activates the nucleolar stress-p53 axis.