SUBNUCLEAR LOCALIZATION OF WT1 IN SPLICING OR TRANSCRIPTION FACTOR DOMAINS IS REGULATED BY ALTERNATIVE SPLICING

WT1 is a tumor suppressor gene with a key role in urogenital developme nt and the pathogenesis of Wilms' tumor. Two alternative splice sites in the WT1 transcript allow the gene to encode four proteins. These ca rry four Kruppel-type zinc fingers and to date have primarily been imp licated in transcriptional control of genes involved in growth regulat ion. However, here we demonstrate colocalization of WT1 with splicing factors in the fetal kidney and testis and in expressing cell lines. U sing immunoprecipitation, we show that two WT1 isoforms directly assoc iate with one or a limited number of components in the spliceosomes an d coiled bodies. Moreover, COS cell expression studies suggest that al ternative splicing within the WT1 zinc finger region determines whethe r the protein localizes mainly with splicing factors or with DNA in tr anscription factor domains in the nucleus. We propose that WT1 plays r oles in posttranscriptional processing of RNA as well as in transcript ion.