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

Martina Niksic1, Joan Slight, Jeremy R Sanford

  • 1MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK.

Human Molecular Genetics
|December 19, 2003
PubMed

Insights

The Wilms' tumour-1 (WT1) protein, linked to kidney cancer, is found in the cytoplasm and associated with RNA, suggesting new roles in gene expression and translation regulation.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Mutations in the Wilms' tumour-1 (WT1) gene are associated with childhood kidney cancer, nephropathy, and gonadal dysgenesis.
  • WT1 protein is essential for developing the genitourinary tract, heart, spleen, and adrenal glands, but its molecular functions remain unclear.
  • WT1 protein is primarily nuclear, with isoforms (-KTS and +KTS) implicated in transcription and RNA processing.

Purpose of the Study:

  • To investigate the subcellular localization and molecular interactions of the WT1 protein.
  • To explore potential novel functions of WT1 beyond its known nuclear roles in gene regulation.

Main Methods:

  • Western blot analysis to detect WT1 protein in different cellular compartments.
  • Identification of WT1 association with ribonucleoprotein particles (RNPs).
  • Analysis of WT1 association with actively translating polysomes.

Main Results:

  • WT1 protein exhibits shuttling between the nucleus and cytoplasm, with cytoplasmic levels varying by cell type (10-50%).
  • A significant portion of cytoplasmic WT1 is associated with RNPs, supporting its role in RNA metabolism.
  • WT1 is found associated with actively translating polysomes, indicating a potential role in translation regulation.
  • Both -KTS and +KTS WT1 isoforms share these shuttling and polysome association properties.

Conclusions:

  • WT1 protein has a novel nucleocytoplasmic shuttling property.
  • WT1's association with RNPs and polysomes suggests expanded roles in RNA metabolism and translation.
  • Both major WT1 isoforms are involved in these newly identified cytoplasmic functions.

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