GENETIC ENHANCEMENT OF RNA-PROCESSING DEFECTS BY A DOMINANT MUTATION IN B52, THE DROSOPHILA GENE FOR AN SR PROTEIN SPLICING FACTOR

SR proteins are essential for pre-mRNA splicing in vitro, act early in the splicing pathway, and can influence alternative splice site choic e. Here we describe the isolation of both dominant and loss-of-functio n alleles of B52, the gene for a Drosophila SR protein. The allele B52 (ED) was identified as a dominant second-site enhancer of white-aprico t (w(a)lpha), a retrotransposon insertion in the second intron of the eye pigmentation gene white with a complex RNA-processing defect. B52( ED) also exaggerates the mutant phenotype of a distinct white allele c arrying a 5' splice site mutation (W-DR18), and alters the pattern of sex-specific splicing at doublesex under sensitized conditions, so tha t the male-specific splice is favored. In addition to being a dominant enhancer of these RNA-processing defects, B52(ED) is a recessive leth al allele that fails to complement other lethal alleles of B52. Compar ison of B52(ED) with the B52(+) allele from which it was derived revea led a single change in a conserved amino acid in the beta 4 strand of the first RNA-binding domain of B52, which suggests that altered RNA b inding is responsible for the dominant phenotype. Reversion of the B52 (ED) dominant allele with X rays led to the isolation of a B52 null al lele. Together, these results indicate a critical role for the SR prot ein B52 in pre-mRNA splicing in vivo.