WT1 interacts with the splicing factor U2AF65 in an isoform-dependent manner and can be incorporated into spliceosomes.
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.
Davies
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RC
Medical Research Council (MRC) Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, UK.
Calvio
C
C
Bratt
E
E
Larsson
S H
SH
Lamond
A I
AI
Hastie
N D
ND
D017398:Alternative Splicing; D000818:Animals; D019556:COS Cells; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016162:Genes, Wilms Tumor; D006801:Humans; D008297:Male; D009687:Nuclear Proteins; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D012261:Ribonucleoproteins / Q000378:metabolism*; D017381:Spliceosomes / Q000378:metabolism*; D000072668:Splicing Factor U2AF; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014407:Tumor Cells, Cultured; D025721:WT1 Proteins
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D012261:Ribonucleoproteins; D000072668:Splicing Factor U2AF; D014157:Transcription Factors; C000607494:U2AF2 protein, human; D025721:WT1 Proteins