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Human Molecular Genetics Advance Access originally published online on December 17, 2003
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Human Molecular Genetics, 2004, Vol. 13, No. 4 463-471
DOI: 10.1093/hmg/ddh040

The Wilms' tumour protein (WT1) shuttles between nucleus and cytoplasm and is present in functional polysomes

Martina Niksic, Joan Slight, Jeremy R. Sanford, Javier F. Caceres and Nicholas D. Hastie*

MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK

Received December 2, 2003; Accepted December 9, 2003

Mutations of the Wilms' tumour-1 (WT1) gene in humans can lead to childhood kidney cancer, life-threatening glomerular nephropathy and gonadal dysgenesis. The WT1 protein is normally expressed in the developing genitourinary tract, heart, spleen and adrenal glands and is crucial for their development, however it's function at the molecular level is yet to be fully understood. The protein is predominantly nuclear and there is evidence that the two different isoforms of WT1 (–KTS and +KTS) are involved in two different steps of gene expression control: transcription and RNA processing. In this study we report a novel property of WT1, namely that it shuttles between the nucleus and cytoplasm. Moreover, western blot analysis showed that between 10 and 50% of total cellular WT1 can be detected in the cytoplasm depending on the cell type. A significant proportion of cytoplasmic WT1 is in association with ribonucleoprotein particles (RNPs), which strengthens the idea of its involvement in RNA metabolism. Furthermore, we report that WT1 is associated with actively translating polysomes, extending even further the potential roles of WT1 and opening the possibility that it is involved in the regulation of translation. Interestingly, despite the functional differences between two of the WT1 isoforms (+/–KTS) within the nucleus, both isoforms share the shuttling property and are found in translating polysomes.

* To whom correspondence should be addressed. Tel: +44 1313322471; Fax: +44 1314678456; Email: nick.hastie{at}hgu.mrc.ac.uk


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