Fig. 5. Diagram for bidirectional control of IKBKAP-FD exon 20 by small molecules.

a SRSF6 binding at the ISE is a major factor in the therapeutic splicing environment induced by RECTAS treatment. The requirement of CLK1 for this process and the direct interaction between CLK1 and RECTAS implies a steric effect for the activation of cellular CLK1. b For its dependence on CLK1 and SRSF6 for recognition, IKBKAP-FD exon 20 splicing can be controlled in a reverse direction by CLK inhibitor treatment.