hnRNP-U directly interacts with WT1 and modulates WT1 transcriptional activation

The Wilms' tumour suppressor gene, WT1, encodes a zinc-finger protein that is mutated in Wilms' tumours and highly expressed in a wide variety of other malignancies. WT1 is a transcription factor that is likely to have additional, post-transcriptional, regulatory roles, although the molecular mechanisms by which WT1 acts remain poorly understood. We have combined genetic and biochemical approaches to show, that endogenous WT1 binds to heterogeneous nuclear ribonuclear protein U (hnRNP-U), that this interaction does not require any other proteins or nucleic acids, involves the zinc-fingers of WT1 and the middle domain of hnRNP-U, and that hnRNP-U can modulate WT1 transcriptional activation of a bona fide WT1 target gene. These findings increase our knowledge of how WT1 exerts its transcriptional regulatory role and suggests that hnRNP-U may be a candidate Wilms' tumour gene at 1q44.