FIGURE 9.

Model of SMN2 exon 7 splicing modulation by ¹⁰C in the presence of L14 and F14. (A) L14 pathway: L14 leaves ¹⁰C unsequestered and accessible for a long-distance interaction with intronic sequences upstream of the branch point. This arrangement interferes with the catalytic core formation at the 5′ ss of exon 7. Consequently, the competing 5′ ss of exon 6 becomes the favorable substrate for the transesterification reaction leading to exon 7 skipping. (B) F14 pathway: F14 sequesters ¹⁰C and prevents a long-distance interaction with intronic sequences upstream of the branch point. This arrangement favors catalytic core formation at the 5′ ss of exon 7. Consequently, SMN2 exon 7 inclusion is promoted.