WT1 INTERACTS WITH THE SPLICING FACTOR U2AF65 IN AN ISOFORM-DEPENDENTMANNER AND CAN BE INCORPORATED INTO SPLICEOSOMES

WT1 is essential for normal kidney development, and genetic alteration s are associated with Wilms' tumor, Denys Drash (DDS), and Frasier syn dromes. Although generally considered a transcription factor this stud y has revealed that WT1 interacts with an essential splicing factor, U 2AF65, and associates with the splicing machinery. WT1 is alternativel y spliced and isoforms that include three amino acids, KTS, show stron ger interaction with U2AF65 in vitro and better colocalization with sp licing factors in vivo. Interestingly a mutation associated with DDS e nhanced both -KTS WT1 binding to U2AE65 and splicing-factor colocaliza tion. These data illustrate the functional importance of WT1 isoforms and suggest that WT1 plays a role in pre-mRNA splicing.