Biochemical function of female-lethal (2)D/Wilms' tumor suppressor-1-associated proteins in alternative pre-mRNA splicing

Angeles Ortega, Martina Niksic, Angela Bachi, Matthias Wilm, Lucas Sánchez, Nicholas Hastie, Juan Valcárcel

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)3040-7
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number5
DOIs
Publication statusPublished - 31 Jan 2003

Keywords

  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Cloning, Molecular
  • Drosophila Proteins
  • Drosophila melanogaster
  • Humans
  • Kidney Neoplasms
  • Molecular Sequence Data
  • Mutagenesis
  • Nuclear Proteins
  • RNA Precursors
  • Recombinant Fusion Proteins
  • Templates, Genetic
  • Transcription, Genetic
  • WT1 Proteins
  • Wilms Tumor

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