title: Functioning of the Drosophila Wilms'-tumor-1-associated protein homolog, Fl(2)d, in Sex-lethal-dependent alternative splicing.
abstract: fl(2)d, the Drosophila homolog of Wilms'-tumor-1-associated protein (WTAP), regulates the alternative splicing of Sex-lethal (Sxl), transformer (tra), and Ultrabithorax (Ubx). Although WTAP has been found in functional human spliceosomes, exactly how it contributes to the splicing process remains unknown. Here we attempt to identify factors that interact genetically and physically with fl(2)d. We begin by analyzing the Sxl-Fl(2)d protein-protein interaction in detail and present evidence suggesting that the female-specific fl(2)d(1) allele is antimorphic with respect to the process of sex determination. Next we show that fl(2)d interacts genetically with early acting general splicing regulators and that Fl(2)d is present in immunoprecipitable complexes with Snf, U2AF50, U2AF38, and U1-70K. By contrast, we could not detect Fl(2)d complexes containing the U5 snRNP protein U5-40K or with a protein that associates with the activated B spliceosomal complex SKIP. Significantly, the genetic and molecular interactions observed for Sxl are quite similar to those detected for fl(2)d. Taken together, our findings suggest that Sxl and fl(2)d function to alter splice-site selection at an early step in spliceosome assembly.
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Jill K M
authors.initials: JK
authors.lastname: Penn
authors.forename: Patricia
authors.initials: P
authors.lastname: Graham
authors.forename: Girish
authors.initials: G
authors.lastname: Deshpande
authors.forename: Gretchen
authors.initials: G
authors.lastname: Calhoun
authors.forename: Ahmad Sami
authors.initials: AS
authors.lastname: Chaouki
authors.forename: Helen K
authors.initials: HK
authors.lastname: Salz
authors.forename: Paul
authors.initials: P
authors.lastname: Schedl
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics*; D004625:Embryo, Nonmammalian / Q000502:physiology; D005260:Female; D005804:Genes, Lethal; D006801:Humans; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D009396:Wilms Tumor / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C067777:Sxl protein, Drosophila; D025521:Tumor Suppressor Proteins; C410299:fl(2)d protein, Drosophila