The protein Sex-lethal antagonizes the splicing factor U2AF to regulate alternative splicing of transformer pre-mRNA.

摘要: Somatic sexual differentiation in Drosophila melanogaster involves a cascade of regulated splicing events and provides an attractive model system for the analysis alternative mechanisms. The protein Sex-lethal (Sxl) activates female-specific 3' splice site first intron transformer (tra) pre-mRNA while repressing non-sex-specific site. We have developed vitro that recapitulates this regulation manner consistent with genetic, transfection fly transformation studies. Using system, we determined molecular basis switch. Here show Sxl inhibits to (default) by specifically binding its polypyrimidine tract, blocking essential factor U2AF. This enables U2AF activate lower-affinity A 'effector' domain present but absent from accounts different activities these two polypyrimidine-tract-binding proteins: addition effector converts it repressor activator renders unable mediate splice-site switching.