Biochemical function of female-lethal (2)D/Wilms' tumor suppressor-1-associated proteins in alternative pre-mRNA splicing.
Genetic and molecular data have implicated the Drosophila gene female-lethal (2)d (fl (2)d) in alternative splicing regulation of genes involved in sexual determination. Sex-specific splicing is under the control of the female-specific regulatory protein sex-lethal (SXL). Co-immunoprecipitation and mass spectrometry results indicate that SXL and FL (2)D form a complex and that the protein VIRILIZER and a Ran-binding protein implicated in protein nuclear import are also present in complexes containing FL (2)D. A human homolog of FL (2)D was identified and cloned. Interestingly, this gene encodes a protein (WTAP) that was previously found to interact with the Wilms' tumor suppressor-1 (WT1), an isoform of which binds to and co-localizes with splicing factors. Alternative splicing of transformer pre-mRNA, a target of SXL regulation, was affected by immunodepletion of hFL (2)D/WTAP from HeLa nuclear extracts, thus arguing for a biochemical function of FL (2)D/WTAP proteins in splicing regulation.
Ortega
Angeles
A
Gene Expression Programme, European Molecular Biology Laboratory, Heidelberg, Germany.
Niksic
Martina
M
Bachi
Angela
A
Wilm
Matthias
M
Sánchez
Lucas
L
Hastie
Nicholas
N
Valcárcel
Juan
J
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics*; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009687:Nuclear Proteins / Q000235:genetics*; D012322:RNA Precursors / Q000235:genetics*; D011993:Recombinant Fusion Proteins; D013698:Templates, Genetic; D014158:Transcription, Genetic; D025721:WT1 Proteins / Q000378:metabolism; D009396:Wilms Tumor / Q000235:genetics
D029721:Drosophila Proteins; D009687:Nuclear Proteins; D012322:RNA Precursors; D011993:Recombinant Fusion Proteins; D025721:WT1 Proteins; C410299:fl(2)d protein, Drosophila