DOES THE WILMS-TUMOR SUPPRESSOR GENE, WT1, PLAY ROLES IN BOTH SPLICING AND TRANSCRIPTION

The Wilms' tumour suppressor gene (WT1) encodes a protein(s) with 4 zi nc fingers that is essential for the development of the genitourinary system. A considerable body of evidence exists to support the idea tha t WT1 binds DNA and functions as a transcription factor. However, we h ave shown recently by confocal microscopy and immunoprecipitation stud ies that a significant proportion of WT1 is associated with splice fac tors in kidney cell lines, fetal tissues and transfected Cos cells. Di fferent isoforms of WT1 are produced by an alternative splice that lea ds to the presence or absence of a 3 amino acid insertion (KTS) betwee n zinc fingers 3 and 4. We have shown that these different forms local ise differently in the nucleus. The +KTS form mainly localises with sp lice factors, the -KTS form mainly with transcription factors. Here we propose a model to account for these different localisations. Also, w e discuss the possible significance of these findings.