RNA editing in the Wilms' tumor susceptibility gene, WT1.

Rat kidney WTl cDNAs contain either a thymidine or a cytosine residue at position 839. Genomic WTl DNA contains only T*^'. To explain these results, we propose the WTl transcript undergoes RNA editing in which U*^' is converted to C, resulting in the replacement of leucine 280 in WTl by proline. RNA editing at the same nucleotide was observed in WTl cDNAs from human testis. In functional assays, the WTl-leucine^*** polypeptide repressed the EGR-1 promoter in in vitro assays -30% more efficiently than WTl-proline. Edited WTl-C*^^ mRNA was barely detectable in neonatal kidney, whereas adult rat kidneys contained both U*^' and C*^'-WT1 mRNA, suggesting a role for the two protein isoforms in growth and differentiation.