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Vol. 12, No. 20, pp. 3217-3225, October 15, 1998
1 Medical Research Council (MRC) Human Genetics Unit,
Western General Hospital, Edinburgh EH4 2XU, UK;
2 Gene
Expression Programme, European Molecular Biology Laboratory, 69012 Heidelberg, Germany;
3 Karolinska Institute, CMB, Molekylar
Genetik, S-171 77 Stockholm, Sweden;
5 Department of
Biochemistry, University of Dundee, Dundee DD1 4HN, UK
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.
[Key Words: WT1; U2AF65; spliceosome; alternative splicing]
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