FIG. 8.

Model for CUS2 action in preparing U2 snRNP for recruitment to the spliceosome. The U2 allele specificity of CUS2 suppression and enhancement suggests a close interaction with stem IIa, as shown. Newly synthesized U2, U2 snRNA emerging from the splicing pathway, or otherwise misfolded U2 interacts with CUS2 and is refolded. ySF3b and ySF3a are the S. cerevisiae protein complexes homologous to the human splicing factors SF3b and SF3a (39). Protein-protein interactions (35, 39, 43) (Fig. 4) are indicated by small gray boxes. The interaction between CUS2 and PRP11 may assist the recruitment of ySF3a to the U2 snRNP as indicated. The ySF3b subunit labeled “155?” is a yeast open reading frame homologous to a vertebrate SF3b subunit suggested to be SF3b155/SAP155 (58a). Once completely assembled, the U2 snRNP can bind to the commitment complex. Given the interaction between the S. pombe homologs of CUS2 and U2AF (47), CUS2 could have a role in U2 snRNP binding to the commitment complex through MUD2 (1).