Genetic enhancement of RNA-processing defects by a dominant mutation in B52, the Drosophila gene for an SR protein splicing factor.

TitleGenetic enhancement of RNA-processing defects by a dominant mutation in B52, the Drosophila gene for an SR protein splicing factor.
Publication TypeJournal Articles
Year of Publication1995
AuthorsPeng X, Mount SM
JournalMol Cell Biol
Volume15
Issue11
Pagination6273-82
Date Published1995 Nov
ISSN0270-7306
KeywordsAlleles, Amino Acid Sequence, Animals, Base Sequence, DNA Primers, Drosophila melanogaster, Drosophila Proteins, Frameshift Mutation, Genes, Dominant, Genes, Insect, Molecular Sequence Data, Nuclear Proteins, Phosphoproteins, Point Mutation, Protein Structure, Tertiary, Proteins, RNA Splicing, RNA-Binding Proteins, Sequence Deletion, Sex Determination Analysis
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.

Alternate JournalMol. Cell. Biol.
PubMed ID7565780
PubMed Central IDPMC230879
Grant ListGM37991 / GM / NIGMS NIH HHS / United States