Figure 8. Model of splicing modulator interaction with the SF3b complex at the BPA-binding pocket constituted by PHF5A and SF3B1.
The molecular surface representation of the protein complex SF3B1 (yellow), PHF5A (blue) and SF3B3 (orange). The intron RNA is shown as red ribbon, with branch point adenosine (BPA) in dark blue. The common splicing modulators binding site is indicated by a star with the approximate positions of the surrounding residues for which resistance mutations were identified. The figure was generated using the yeast Bact complex coordinates. The schematic model indicates the inverse correlation between the GC content of the intron sequence and their resistance to splicing modulation. Specifically, high GC content intron substrates are weaker substrates that show more sensitivity or less resistance to splicing modulators.