The ARHGAP10-202aa protein encoded by circARHGAP10 promotes skeletal muscle development and regeneration

Muscle growth and development are fundamental biological processes with significant implications for both human health and livestock production. Although circular RNAs (circRNAs) have long been regarded as noncoding RNAs, recent studies suggest that some circRNAs possess protein-coding potential. However, the biological roles and mechanisms of circRNA-encoded proteins remain poorly understood. Here, we identify circARHGAP10 as a protein-coding circRNA in cattle skeletal muscle that encodes a 202-amino acid protein, ARHGAP10-202aa, through an internal ribosome entry site (IRES)-dependent mechanism. ARHGAP10-202aa expression is confirmed by in vitro translation, immunodetection with a specific antibody, and Western blotting analysis. Functional assays reveal that ARHGAP10-202aa interacts with myosin light chain 6 (MYL6) to promote myoblast differentiation. Moreover, in vivo overexpression of ARHGAP10-202aa significantly enhances MYL6 expression and accelerates the regeneration of injured tibialis anterior muscle in mice. These findings not only expand our understanding of the role of circRNAs in muscle biology but also underscore the functional significance of circRNA-encoded proteins in muscle recovery and regeneration.