SPECIFIC INTERACTIONS BETWEEN PROTEINS IMPLICATED IN SPLICE-SITE SELECTION AND REGULATED ALTERNATIVE SPLICING

Specific recognition and pairing of the 5' and 3' splice sites are cri tical 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 U1-70K) and with the 35 kd subunit of the splicing factor U2AF (U2AF35). Previous studies indicated that th e U1 snRNP binds specifically to the 5' splice site, while U2AF35-U2AF 65 heterodimer binds to the 3' splice site. Together, these observatio ns suggest that SC35 and other members of the SR family of splicing fa ctors may function in splice site selection by acting as a bridge betw een components bound to the 5' and 3' splice sites. Interestingly, SC3 5, SF2/ASF, and U2AF35 also interact with the Drosophila splicing regu lators Transformer (Tra) and Transformer-2 (Tra2), suggesting that pro tein-protein interactions mediated by SR proteins may also play an imp ortant role in regulating alternative splicing.