Does the Wilms' tumour suppressor gene, WT1, play roles in both splicing and transcription?

Abstract

The Wilms' tumour suppressor gene (WT1) encodes a protein(s) with 4 zinc fingers that is essential for the development of the genitourinary system. A considerable body of evidence exists to support the idea that WT1 binds DNA and functions as a transcription factor. However, we have shown recently by confocal microscopy and immunoprecipitation studies that a significant proportion of WT1 is associated with splice factors in kidney cell lines, fetal tissues and transfected Cos cells. Different isoforms of WT1 are produced by an alternative splice that leads to the presence or absence of a 3 amino acid insertion (KTS) between zinc fingers 3 and 4. We have shown that these different forms localise differently in the nucleus. The +KTS form mainly localises with splice factors, the -KTS form mainly with transcription factors. Here we propose a model to account for these different localisations. Also, we discuss the possible significance of these findings.