title: Protein phosphorylation plays an essential role in the regulation of alternative splicing and sex determination in Drosophila.
abstract: Alternative mRNA splicing directed by SR proteins and the splicing regulators TRA and TRA2 is an essential feature of Drosophila sex determination. These factors are highly phosphorylated, but the role of their phosphorylation in vivo is unclear. We show that mutations in the Drosophila LAMMER kinase, Doa, alter sexual differentiation and interact synergistically with tra and tra2 mutations. Doa mutations disrupt sex-specific splicing of doublesex pre-mRNA, a key regulator of sex determination, by affecting the phosphorylation of one or more proteins in the female-specific splicing enhancer complex. Examination of pre-mRNAs regulated similarly to dsx shows that the requirement for Doa is substrate specific. These results demonstrate that a SR protein kinase plays a specific role in developmentally regulated alternative splicing.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha 68198, USA.
authors.forename: C
authors.initials: C
authors.lastname: Du
authors.forename: M E
authors.initials: ME
authors.lastname: McGuffin
authors.forename: B
authors.initials: B
authors.lastname: Dauwalder
authors.forename: L
authors.initials: L
authors.lastname: Rabinow
authors.forename: W
authors.initials: W
authors.lastname: Mattox
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D004330:Drosophila / Q000235:genetics* / Q000502:physiology; D029721:Drosophila Proteins; D005260:Female; D018507:Gene Expression Regulation, Developmental; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D012322:RNA Precursors / Q000235:genetics; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000378:metabolism; D012261:Ribonucleoproteins / Q000378:metabolism; D000068103:Serine-Arginine Splicing Factors; D019849:Sex Determination Processes; D012733:Sex Differentiation / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C070369:DSX protein, Drosophila; D029721:Drosophila Proteins; D019476:Insect Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; C083909:RBP1 protein, Drosophila; D012322:RNA Precursors; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; C491388:SRSF3 protein, human; C066174:tra2 protein, Drosophila; D000068103:Serine-Arginine Splicing Factors; C089977:Doa protein, Drosophila; D017346:Protein Serine-Threonine Kinases