SRSF10 Plays a Role in Myoblast Differentiation and Glucose Production via Regulation of Alternative Splicing

• The splicing factor SRSF10 is required for myoblast differentiation
• SRSF10 regulates muscle-specific splicing of Lrrfip1 pre-mRNA
• SRSF10 mediates glucose production both in cells and in mice
• PGC1α is a key target of SRSF10 during glucose production

SummaryAlternative splicing is a major mechanism of controlling gene expression and protein diversity in higher eukaryotes. We report that the splicing factor SRSF10 functions during striated muscle development, myoblast differentiation, and glucose production both in cells and in mice. A combination of RNA-sequencing and molecular analysis allowed us to identify muscle-specific splicing events controlled by SRSF10 that are critically involved in striated muscle development. Inclusion of alternative exons 16 and 17 of Lrrfip1 is a muscle-specific event that is activated by SRSF10 and essential for myoblast differentiation. On the other hand, in mouse primary hepatocytes, PGC1α is a key target of SRSF10 that regulates glucose production by fasting. SRSF10 represses inclusion of PGC1α exon 7a and facilitates the production of functional protein. The results highlight the biological significance of SRSF10 and regulated alternative splicing in vivo.

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