RNA editing in the Wilms' tumor susceptibility gene, WT1

Rat kidney WT1 cDNAs contain either a thymidine or a cytosine residue at position 839. Genomic WT1 DNA contains only T⁸³⁹. To explain these results, we propose the WT1 transcript undergoes RNA editing in which U⁸³⁹ is converted to C, resulting in the replacement of leucine 280 in WT1 by proline. RNA editing at the same nucleotide was observed in WT1 cDNAs from human testis. In functional assays, the WT1-leucine²⁸⁰ polypeptide repressed the EGR-1 promoter in in vitro assays ~30% more efficiently than WT1-proline. Edited WT1-C⁸³⁹ mRNA was barely detectable in neonatal kidney, whereas adult rat kidneys contained both U⁸³⁹ and C⁸³⁹-WT1 mRNA, suggesting a role for the two protein isoforms in growth and differentiation.