Nucleic Acids Research, Vol 26, Issue 7 1784-1792, Copyright © 1998 by Oxford University Press
N Bardeesy and J Pelletier
The Wilms' tumour suppressor gene (wt1) is mutated in a subset of patients
with Wilms' tumour and has a critical role in urogenital development. wt1
encodes a zinc finger transcription factor which regulates expression of
several genes involved in cellular proliferation and differentiation.
Although a number of studies have characterized the DNA binding properties
of the WT1 protein, recent evidence has suggested that WT1 may also have a
role in RNA metabolism. We have used an RNA selection method to identify
WT1 binding ligands from a random RNA pool. Three groups of RNA ligands
specifically recognized by WT1 were identified. Mutational analysis
pinpointed ribonucleotide sequences critical for binding. Analysis of
truncated WT1 proteins demonstrated that three of four zinc fingers were
necessary for RNA-protein interaction. The naturally occurring WT1 isoforms
with insertion of lysine, threonine and serine between zinc fingers three
and four were unable to bind the selected RNAs. The selected RNA ligands
competed with the cognate WT1 DNA binding site for complex formation with
WT1. Our findings suggest potential cellular RNA target sequences for WT1
and provide tools for studying the structural and functional properties of
this tumour suppressor protein.
ARTICLES
Overlapping RNA and DNA binding domains of the wt1 tumor suppressor gene product
Department of Biochemistry, McGill University, 3655 Drummond Street, Montreal, Quebec H3G 1Y6, Canada.
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