Figure 2.

Intron definition model for splicing of SMN exon 7. As per intron definition model, both splice sites of an intron could be defined without participation of a cross-exon interaction. Shown are splicing cis-elements and transacting factors that affect intron 7 definition. These include ISS-N1, GC-rich, Element 2 and hnRNP A1 and TIA1 motifs.²⁵,²⁷,⁵⁵,⁵⁶,⁶² (+) indicates that a given cis-element or splicing factor promotes exon 7 inclusion. Supporting intron definition model, binding of TIA1 to URC1/URC2 within intron 7 brings a change in the context leading to recruitment of U1 snRNP at the 5′ ss of exon 7. Similar stimulatory changes and a forced intron 7 definition could be brought about by ASOs targeting ISS-N1 or GC-rich sequence.²⁷,⁵⁵