RNA binding by the Wilms tumor suppressor zinc finger proteins.

• DOI: 10.1073/pnas.93.15.7562
• Publication Date: 2002-07-26T14:43:20Z
• Authors: A Caricasole; A Duarte; S H Larsson; N D Hastie; M Little; G Holmes; I Todorov; A Ward
• Keywords: 0301 basic medicine; Genes, Wilms Tumor; Locus; Recombinant Fusion Proteins; Wt1 Gene; Molecular Sequence Data; posttranscriptional regulation; 612; Immediate-Early Proteins; Mice; 03 medical and health sciences; Insulin-Like Growth Factor II; Sequence; Consensus Sequence; Animals; Humans; Rats, Inbred BUF; Factor-a-Chain; Early Growth Response Protein 1; Modulation; Binding Sites; Base Sequence; Chromosomes, Human, Pair 11; RNA-Binding Proteins; Exons; Kidney Neoplasms; Rats; DNA-Binding Proteins; Growth Factor-II; insulin-like growth factor II; 1000 General; gene expression; Domains; RNA; early growth response factor 1; Promoters; Gene-Product; Transcriptional Repression

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.