Schematic model of the interplay between SRSF3, SRSF10, SRSF12, and TRA2 proteins in the control of CLK1 exon 4 splicing. When the demand for active CLK1 is high (e.g., when SRSF3, SRSF10, and SRSF12 are dephosphorylated [i.e., dSRSFR3, dSRSF10, and dSRSF12]), exon 4 inclusion would rely on TRA2 proteins to act through the exonic enhancer. The existence of phosphorylated SRSF3 (but not of phosphorylated SRSF12 or SRSF10) would create a competition between TRA2-mediated activation and SRSF3-mediated repression, here occurring at the 3′ splice site of exon 4, to produce intermediate levels of active CLK1. Phosphorylated SRSF10 and SRSF12 would associate with TRA2 proteins to interfere with the enhancer activity, allowing SRSF3 to repress exon 4 inclusion more efficiently.
