ANTISENSE WT1 TRANSCRIPTION PARALLELS SENSE MESSENGER-RNA AND PROTEINEXPRESSION IN FETAL KIDNEY AND CAN ELEVATE PROTEIN-LEVELS IN-VITRO

Recent studies have identified antisense WT1 mRNAs whose expression is regulated by a promoter located in the first intron of the WT1 gene. Transcription directed by the antisense promoter is positively autoreg ulated by the WT1 protein implicating the antisense RNA in the control of WT1 gene expression. To elucidate further the biological role of t he antisense RNA in the developing kidney, its distribution of express ion has been examined relative to WT1 sense mRNA and WT1 protein, Usin g strand-specific WT1 riboprobes, the expression of WT1 and the antise nse message mere examined by in situ hybridization in the developing h uman fetal kidney at different gestational ages, The expression of the antisense strand was strongest in the podocytes and glomeruli and als o in the S-form nephrons and the condensing blastema in the developing kidney. Expression was also seen in the podocytes of the mature kidne y, The WT1 protein and sense mRNA for WT1 also showed a similar patter n, suggesting that the antisense transcript does not function simply a s a downregulator of protein production. Expression of antisense WT1 t ron 1 in cells constitutively producing high levels of WT1 also demons trated no downregulation of protein and in most casts actually showed upregulated WT1 protein expression. These results strongly suggest tha t WT1 antisense transcripts positively modulate WT1 protein levels irt vivo. (C) 1998 John Wiley & Sons, Ltd.