title: Genetic enhancement of RNA-processing defects by a dominant mutation in B52, the Drosophila gene for an SR protein splicing factor.
abstract: SR proteins are essential for pre-mRNA splicing in vitro, act early in the splicing pathway, and can influence alternative splice site choice. Here we describe the isolation of both dominant and loss-of-function alleles of B52, the gene for a Drosophila SR protein. The allele B52ED was identified as a dominant second-site enhancer of white-apricot (wa), a retrotransposon insertion in the second intron of the eye pigmentation gene white with a complex RNA-processing defect. B52ED also exaggerates the mutant phenotype of a distinct white allele carrying a 5' splice site mutation (wDR18), and alters the pattern of sex-specific splicing at doublesex under sensitized conditions, so that the male-specific splice is favored. In addition to being a dominant enhancer of these RNA-processing defects, B52ED is a recessive lethal allele that fails to complement other lethal alleles of B52. Comparison of B52ED with the B52+ allele from which it was derived revealed 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 binding is responsible for the dominant phenotype. Reversion of the B52ED dominant allele with X rays led to the isolation of a B52 null allele. Together, these results indicate a critical role for the SR protein B52 in pre-mRNA splicing in vivo.
authors.affiliation: Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
authors.forename: X
authors.initials: X
authors.lastname: Peng
authors.forename: S M
authors.initials: SM
authors.lastname: Mount
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics*; D016368:Frameshift Mutation; D005799:Genes, Dominant; D017344:Genes, Insect; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D010750:Phosphoproteins; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000502:physiology*; D012326:RNA Splicing; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000502:physiology*; D017384:Sequence Deletion; D012732:Sex Determination Analysis
chemical_list: D017931:DNA Primers; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; C070791:B52 protein, Drosophila