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Science 10 July 1992:
Vol. 257. no. 5067, pp. 235 - 237
DOI: 10.1126/science.1321494
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Articles

Science, Vol 257, Issue 5067, 235-237
Copyright © 1992 by American Association for the Advancement of Science

articles

Modulation of DNA binding specificity by alternative splicing of the Wilms tumor wt1 gene transcript

WA Bickmore, K Oghene, MH Little, A Seawright, V van Heyningen, and ND Hastie

Medical Research Council Human Genetics Unit, Western General Hospital, Edinburgh, Scotland.

The technique of whole-genome polymerase chain reaction was used to study the DNA binding properties of the product of the wt1 gene. The zinc finger region of this gene is alternatively spliced such that the major transcript encodes a protein with three extra amino acids between the third and fourth fingers. The minor form of the protein binds specifically to DNA. It is now shown that the major form of wt1 messenger RNA encodes a protein that binds to DNA with a specificity that differs from that of the minor form. Therefore, alternative splicing within the DNA binding domain of a transcription factor can generate proteins with distinct DNA binding specificities and probably different physiological targets.


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Identification of WTAP, a novel Wilms' tumour 1-associating protein.
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The Wilms' Tumor Suppressor, WT1, Inhibits 12-O-Tetradecanoylphorbol-13-acetate Activation of the Multidrug Resistance-1 Promoter.
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Tumor-associated WT1 Missense Mutants Indicate That Transcriptional Activation by WT1 Is Critical for Growth Control.
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J. Biol. Chem. 274, 13258-13263
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WT1 interacts with the splicing factor U2AF65 in an isoform-dependent manner and can be incorporated into spliceosomes.
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Expression of the Three Alternative Forms of the Sphingolipid Activator Protein Precursor in Baby Hamster Kidney Cells and Functional Assays in a Cell Culture System.
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The WT1 gene product stabilizes p53 and inhibits p53-mediated apoptosis..
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Repression of Pax-2 by WT1 during normal kidney development.
G Ryan, V Steele-Perkins, J. Morris, F. Rauscher, and G. Dressler (1995)
Development 121, 867-875
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A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1.
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Science 266, 66-71
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RNA editing in the Wilms' tumor susceptibility gene, WT1..
P M Sharma, M Bowman, S L Madden, F J Rauscher, and S Sukumar (1994)
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WT1-mediated growth suppression of Wilms tumor cells expressing a WT1 splicing variant.
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Multiple zinc finger forms resulting from developmentally regulated alternative splicing of a transcription factor gene.
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