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Proc Natl Acad Sci U S A. Nov 1, 1991; 88(21): 9618–9622.
PMCID: PMC52769

Alternative splicing and genomic structure of the Wilms tumor gene WT1.

Abstract

The chromosome 11p13 Wilms tumor susceptibility gene WT1 appears to play a crucial role in regulating the proliferation and differentiation of nephroblasts and gonadal tissue. The WT1 gene consists of 10 exons, encoding a complex pattern of mRNA species: four distinct transcripts are expressed, reflecting the presence or absence of two alternative splices. Splice I consists of a separate exon, encoding 17 amino acids, which is inserted between the proline-rich amino terminus and the zinc finger domains. Splice II arises from the use of an alternative 5' splice junction and results in the insertion of 3 amino acids between zinc fingers 3 and 4. RNase protection analysis demonstrates that the most prevalent splice variant in both human and mouse is that which contains both alternative splices, whereas the least common is the transcript missing both splices. The relative distribution of splice variants is highly conserved between normal fetal kidney tissue and Wilms tumors that have intact WT1 transcripts. The ratio of these different WT1 mRNA species is also maintained as a function of development in the mouse kidney and in various mouse tissues expressing WT1. The conservation in structure and relative levels of each of the four WT1 mRNA species suggests that each encoded polypeptide makes a significant contribution to normal gene function. The control of cellular proliferation and differentiation exerted by the WT1 gene products may involve interactions between four polypeptides with distinct targets and functions.

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  • Call KM, Glaser T, Ito CY, Buckler AJ, Pelletier J, Haber DA, Rose EA, Kral A, Yeger H, Lewis WH, et al. Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus. Cell. 1990 Feb 9;60(3):509–520. [PubMed]
  • Gessler M, Poustka A, Cavenee W, Neve RL, Orkin SH, Bruns GA. Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping. Nature. 1990 Feb 22;343(6260):774–778. [PubMed]
  • Haber DA, Buckler AJ, Glaser T, Call KM, Pelletier J, Sohn RL, Douglass EC, Housman DE. An internal deletion within an 11p13 zinc finger gene contributes to the development of Wilms' tumor. Cell. 1990 Jun 29;61(7):1257–1269. [PubMed]
  • Pritchard-Jones K, Fleming S, Davidson D, Bickmore W, Porteous D, Gosden C, Bard J, Buckler A, Pelletier J, Housman D, et al. The candidate Wilms' tumour gene is involved in genitourinary development. Nature. 1990 Jul 12;346(6280):194–197. [PubMed]
  • Buckler AJ, Pelletier J, Haber DA, Glaser T, Housman DE. Isolation, characterization, and expression of the murine Wilms' tumor gene (WT1) during kidney development. Mol Cell Biol. 1991 Mar;11(3):1707–1712. [PMC free article] [PubMed]
  • Knudson AG, Jr, Strong LC. Mutation and cancer: a model for Wilms' tumor of the kidney. J Natl Cancer Inst. 1972 Feb;48(2):313–324. [PubMed]
  • Huff V, Miwa H, Haber DA, Call KM, Housman D, Strong LC, Saunders GF. Evidence for WT1 as a Wilms tumor (WT) gene: intragenic germinal deletion in bilateral WT. Am J Hum Genet. 1991 May;48(5):997–1003. [PMC free article] [PubMed]
  • Ton CC, Huff V, Call KM, Cohn S, Strong LC, Housman DE, Saunders GF. Smallest region of overlap in Wilms tumor deletions uniquely implicates an 11p13 zinc finger gene as the disease locus. Genomics. 1991 May;10(1):293–297. [PubMed]
  • Cowell JK, Wadey RB, Haber DA, Call KM, Housman DE, Pritchard J. Structural rearrangements of the WT1 gene in Wilms' tumour cells. Oncogene. 1991 Apr;6(4):595–599. [PubMed]
  • Sukhatme VP, Cao XM, Chang LC, Tsai-Morris CH, Stamenkovich D, Ferreira PC, Cohen DR, Edwards SA, Shows TB, Curran T, et al. A zinc finger-encoding gene coregulated with c-fos during growth and differentiation, and after cellular depolarization. Cell. 1988 Apr 8;53(1):37–43. [PubMed]
  • Joseph LJ, Le Beau MM, Jamieson GA, Jr, Acharya S, Shows TB, Rowley JD, Sukhatme VP. Molecular cloning, sequencing, and mapping of EGR2, a human early growth response gene encoding a protein with "zinc-binding finger" structure. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7164–7168. [PMC free article] [PubMed]
  • Rauscher FJ, 3rd, Morris JF, Tournay OE, Cook DM, Curran T. Binding of the Wilms' tumor locus zinc finger protein to the EGR-1 consensus sequence. Science. 1990 Nov 30;250(4985):1259–1262. [PubMed]
  • Mitchell PJ, Tjian R. Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. Science. 1989 Jul 28;245(4916):371–378. [PubMed]
  • Pelletier J, Schalling M, Buckler AJ, Rogers A, Haber DA, Housman D. Expression of the Wilms' tumor gene WT1 in the murine urogenital system. Genes Dev. 1991 Aug;5(8):1345–1356. [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PMC free article] [PubMed]
  • Breitbart RE, Andreadis A, Nadal-Ginard B. Alternative splicing: a ubiquitous mechanism for the generation of multiple protein isoforms from single genes. Annu Rev Biochem. 1987;56:467–495. [PubMed]
  • Morishita K, Parganas E, Douglass EC, Ihle JN. Unique expression of the human Evi-1 gene in an endometrial carcinoma cell line: sequence of cDNAs and structure of alternatively spliced transcripts. Oncogene. 1990 Jul;5(7):963–971. [PubMed]
  • Bordereaux D, Fichelson S, Tambourin P, Gisselbrecht S. Alternative splicing of the Evi-1 zinc finger gene generates mRNAs which differ by the number of zinc finger motifs. Oncogene. 1990 Jun;5(6):925–927. [PubMed]
  • Benezra R, Davis RL, Lockshon D, Turner DL, Weintraub H. The protein Id: a negative regulator of helix-loop-helix DNA binding proteins. Cell. 1990 Apr 6;61(1):49–59. [PubMed]
  • Yandell DW, Campbell TA, Dayton SH, Petersen R, Walton D, Little JB, McConkie-Rosell A, Buckley EG, Dryja TP. Oncogenic point mutations in the human retinoblastoma gene: their application to genetic counseling. N Engl J Med. 1989 Dec 21;321(25):1689–1695. [PubMed]
  • Orita M, Iwahana H, Kanazawa H, Hayashi K, Sekiya T. Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2766–2770. [PMC free article] [PubMed]

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