TY - JOUR T1 - Genetic enhancement of RNA-processing defects by a dominant mutation in B52, the Drosophila gene for an SR protein splicing factor. JF - Mol Cell Biol Y1 - 1995 A1 - Peng, X A1 - Mount, S M KW - Alleles KW - Amino Acid Sequence KW - Animals KW - Base Sequence KW - DNA Primers KW - Drosophila melanogaster KW - Drosophila Proteins KW - Frameshift Mutation KW - Genes, Dominant KW - Genes, Insect KW - Molecular Sequence Data KW - Nuclear Proteins KW - Phosphoproteins KW - Point Mutation KW - Protein Structure, Tertiary KW - Proteins KW - RNA Splicing KW - RNA-Binding Proteins KW - Sequence Deletion KW - Sex Determination Analysis AB -

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.

VL - 15 CP - 11 ER -