Research Papers

WT1 interacts with the splicing protein RBM4 and regulates its ability to modulate alternative splicing in vivo

Exp. Cell Res. 312: 3379-3388 (2006) - PMID: 16934801 ()
Authors: Markus MA, Heinrich B, Raitskin O, Adams DJ, Mangs H, Goy C, Ladomery M, Sperling R, Stamm S, Morris BJ.


Wilms tumour protein 1 (WT1), a protein implicated in various cancers and developmental disorders, consists of two major isoforms: KTS”>WT1, a transcription factor, and WT1, a posttranscriptional regulator that binds to RNA and can interact with splicing components. Here we show that WT1 interacts with the novel splicing regulator RBM4. Each protein was found to co-localize in nuclear speckles and to co-sediment with supraspliceosomes in glycerol gradients. RBM4 conferred dose-dependent and cell-specific regulation of alternative splicing of pre-mRNAs transcribed from several minigenes. We found that overexpressed WT1 abrogated this effect of RBM4 on splice-site selection, whereas KTS”>WT1 did not. We conclude that the (+KTS) form of WT1 is able to inhibit the effect of RBM4 on alternative splicing.

Keywords: Alternative splicing; RNA binding proteins; speckles; Wilms tumour suppressor; supraspliceosome