RNA-BINDING BY THE WILMS-TUMOR SUPPRESSOR ZINC-FINGER PROTEINS

The Wilms tumor suppressor gene WT1 is implicated in the ontogeny of g enito-urinary abnormalities, including Denys-Drash syndrome and Wilms tumor of the kidney. WT1 encodes Kruppel-type zinc finger proteins tha t can regulate the expression of several growth-related genes, apparen tly by binding to specific DNA sites located within 5' untranslated le ader regions as well as 5' promoter sequences. Both WT1 and a closely related early growth response factor, EGR1, can bind the same DNA sequ ences 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 RN A sequences, and that the zinc fingers are required for this interacti on. 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 o f WT1 proteins is shown to be RNase, but not DNase, sensitive. Therefo re, WT1 might, like the Kruppel-type zinc finger protein TFIIIA, regul ate gene expression by both transcriptional and posttranscriptional me chanisms.