Specific interactions between proteins implicated in splice site selection and regulated alternative splicing

Abstract

Specific recognition and pairing of the 5′ and 3′ splice sites are critical steps in pre-mRNA splicing. We report that the splicing factors SC35 and SF2 ASF specifically interact with both the integral U1 small nuclear ribonucleoprotein (snRNP U1-70K0 and with the 35 kd subunit of the splicing factor U2AF (U2AF 35). Previous studies indicated that the U1 snRNP binds specifically to the 5′ splice site, while U2AF 35-U2AF 35 heterodimer binds to the 3′ splice site. Together, these observations suggest that SC35 and other members of the SR family of splicing factors may function in splice site selection by acting as a bridge between components bound to the 5′ and 3′ splice sites. Interestingly, SC35, SF2 ASF , and U2AF 35 also interact with the Drosophila splicing regulators Transformer (Tra) and Transformer-2 (Tra2), suggesting that protein-protein interactions mediated by SR proteins may also play an important role in regulating alternative splicing.