Splicing Factor SRSF1 Is Essential for Satellite Cell Proliferation and Postnatal Maturation of Neuromuscular Junctions in Mice

Summary Satellite cells are main muscle stem cells that could provide myonuclei for myofiber growth and synaptic-specific gene expression during the early postnatal development. Here, we observed that splicing factor SRSF1 is highly expressed in myoblasts and its expression is closely related with satellite cell activation and proliferation. By genetic deletion of SRSF1 in myogenic progenitors, we found that SRSF1 is critical for satellite cell proliferation in vitro and in vivo. Most notably we also observed that SRSF1 is required for the functional neuromuscular junction (NMJ) formation, as SRSF1-deficient mice fail to form mature pretzel-like NMJs, which leads to muscle weakness and premature death in mice. Finally, we demonstrated that SRSF1 contributes to muscle innervation and muscle development likely by regulating a restricted set of tissue-specific alternative splicing events. Thus, our data define a unique role for SRSF1 in postnatal skeletal muscle growth and function in mice.

Highlights • SRSF1 is highly expressed in activated satellite cells • Loss of SRSF1 dramatically impairs satellite cell proliferation in vitro and in vivo • SRSF1 is also required for the functional neuromuscular junction formation in mice • SRSF1-deficient mice display muscle weakness and die prematurely

In this article, Feng and colleagues show that the splicing factor SRSF1 is highly expressed in activated satellite cells, and its expression is closely related with satellite cell activation and proliferation. SRSF1 is also required for functional neuromuscular junction (NMJ) formation in mice. SRSF1-deficient mice display severe NMJ disorders, muscle weakness, and premature death.