FIG 12.

Possible mechanism for TIA1- and Pcbp1-mediated recruitment of U2 snRNP to the branch point. TIA1 and Pcbp1 interact with each other and bind to the UUUUCCCCCC enhancer elements upstream of the target exon through its RRM2 and KHI domains, respectively. Without TIA1 and Pcbp1 binding, a weak branch point is poorly recognized by U2 snRNP. This prevents A complex formation and results in exon 16 exclusion. When present, TIA1 and Pcbp1 bind to their cognate enhancers and promote recruitment and stabilization of U2 snRNP to a weak branch point via interactions with RBM39, U2AF65, and SF3b155. This stimulates A complex formation and subsequent exon inclusion.