CircMAPK1-encoded micropeptide circMAPK1-110aa inhibits proliferation and differentiation of goat skeletal muscle satellite cells by suppressing MAPK1/3 phosphorylation

Skeletal muscle development directly determines growth efficiency and meat quality in livestock. Circular RNAs (circRNAs) and their encoded micropeptides are emerging regulators of this process, yet their roles in goats remain poorly understood. Through integrated ribosome profiling (Ribo-seq) and circRNA-seq of goat skeletal muscle satellite cells (SMSCs), we identified a MAPK1-derived protein-coding circRNA, circMAPK1 (novel-circ-0039015). Functional analyses revealed that circMAPK1 overexpression suppressed SMSCs proliferation and myogenic differentiation. Mechanistically, circMAPK1 encodes a 110-amino-acid micropeptide (circMAPK1-110aa) that binds Mitogen-Activated Protein Kinase Kinase 1 (MAP2K1) and reduces MAPK1/3 phosphorylation, thereby attenuating Mitogen-Activated Protein Kinase (MAPK) signaling. Importantly, pharmacological activation of the MAPK pathway with C16-PAF partially restored muscle cell growth and differentiation. These findings establish circMAPK1 as a negative regulator of goat skeletal muscle development and highlight its encoded micropeptides as a potential molecular target. By uncovering a new regulatory mechanism of muscle growth, this study provides valuable insights for breeding strategies aimed at enhancing meat yield and quality in goats.