RNA binding by the Wilms tumor suppressor zinc finger proteins

A A Caricasole, Antonio Duarte, S H Larsson, N D Hastie, M Little, G Holmes, I T Todorov, A Ward

Research output: Contribution to journalArticlepeer-review

184 Citations (Scopus)

Abstract

The Wilms tumor suppressor gene WT1 is implicated in the ontogeny of genito-urinary abnormalities, including Denys-Drash syndrome and Wilms tumor of the kidney. WT1 encodes Kruppel-type zinc finger proteins that can regulate the expression of several growth-related genes, apparently by binding to specific DNA sites located within 5' untranslated leader regions as well as 5' promoter sequences. Both WT1 and a closely related early growth response factor, EGR1, can bind the same DNA sequences from the mouse gene encoding insulin-like growth factor 2 (Igf-2). We report that WT1, but not EGR1, can bind specific Igf-2 exonic RNA sequences, and that the zinc fingers are required for this interaction. WT1 zinc finger 1, which is not represented in EGR1, plays a more significant role in RNA binding than zinc finger 4, which does have a counterpart in EGR1. Furthermore, the normal subnuclear localization of WT1 proteins is shown to be RNase, but not DNase, sensitive. Therefore, WT1 might, like the Kruppel-type zinc finger protein TFIIIA, regulate gene expression by both transcriptional and posttranscriptional mechanisms.

Original languageEnglish
Pages (from-to)7562-7566
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number15
Publication statusPublished - 23 Jul 1996

Keywords

  • Animals
  • Base Sequence
  • Binding Sites
  • Chromosomes, Human, Pair 11
  • Consensus Sequence
  • DNA-Binding Proteins
  • Early Growth Response Protein 1
  • Exons
  • Genes, Wilms Tumor
  • Humans
  • Immediate-Early Proteins
  • Insulin-Like Growth Factor II
  • Kidney Neoplasms
  • Mice
  • Molecular Sequence Data
  • RNA
  • RNA-Binding Proteins
  • Rats
  • Rats, Inbred BUF
  • Recombinant Fusion Proteins
  • Syndrome
  • Transcription Factors
  • WT1 Proteins
  • Wilms Tumor
  • Zinc Fingers
  • Journal Article
  • Research Support, Non-U.S. Gov't

Fingerprint

Dive into the research topics of 'RNA binding by the Wilms tumor suppressor zinc finger proteins'. Together they form a unique fingerprint.

Cite this