DISTINCT MECHANISMS OF SPLICING REGULATIONS IN-VIVO BY THE DROSOPHILAPROTEIN SEX-LETHAL

The protein Sex-lethal (SXL) controls pre-mRNA splicing of two genes i nvolved in Drosophila sex determination: transformer (a a) and the Sri gene itself. Previous irt vitro results indicated that SXL antagonize s the general splicing factor U2AF(65) to regulate splicing of tra. In this report, we have used transgenic flies expressing chimeric protei ns between SXL and the effector domain of U2AF(65) to study the mechan isms of splicing regulation by SXL in vivo. Conferring U2AF activity t o SXL relieves its inhibitory activity on tra splicing but not on Sri splicing. Therefore, antagonizing U2AF(65) can explain tra splicing re gulation both in vitro and in vivo, but this mechanism cannot explain splicing regulation of Sri pre-mRNA. These results are a direct proof that Sri, the master regulatory gene in sex determination, has multipl e and separable activities in the regulation of pre-mRNA splicing.