WT1 interacts with the splicing factor U2AF65 in an isoform-dependent manner and can be incorporated into spliceosomes
- Rachel C. Davies1,
- Cinzia Calvio2,
- Eva Bratt1,3,
- Stefan H. Larsson1,3,4,
- Angus I. Lamond5, and
- Nicholas D. Hastie1,6
- 1Medical Research Council (MRC) Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, UK; 2Gene Expression Programme, European Molecular Biology Laboratory, 69012 Heidelberg, Germany; 3Karolinska Institute, CMB, Molekylar Genetik, S-171 77 Stockholm, Sweden; 5Department of Biochemistry, University of Dundee, Dundee DD1 4HN, UK
Abstract
WT1 is essential for normal kidney development, and genetic alterations are associated with Wilms’ tumor, Denys Drash (DDS), and Frasier syndromes. Although generally considered a transcription factor this study has revealed that WT1 interacts with an essential splicing factor, U2AF65, and associates with the splicing machinery. WT1 is alternatively spliced and isoforms that include three amino acids, KTS, show stronger interaction with U2AF65 in vitro and better colocalization with splicing factors in vivo. Interestingly a mutation associated with DDS enhanced both −KTS WT1 binding to U2AF65 and splicing-factor colocalization. These data illustrate the functional importance of WT1 isoforms and suggest that WT1 plays a role in pre-mRNA splicing.
