WT1 interacts with the splicing protein RBM4 and regulates its ability to modulate alternative splicing in vivo.
Wilm's tumor protein 1 (WT1), a protein implicated in various cancers and developmental disorders, consists of two major isoforms: WT1(-KTS), a transcription factor, and WT1(+KTS), a post-transcriptional 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 colocalize in nuclear speckles and to cosediment with supraspliceosomes in glycerol gradients. RBM4 conferred dose-dependent and cell-specific regulation of alternative splicing of pre-mRNAs transcribed from several reporter genes. We found that overexpressed WT1(+KTS) abrogated this effect of RBM4 on splice-site selection, whereas WT1(-KTS) did not. We conclude that the (+KTS) form of WT1 is able to inhibit the effect of RBM4 on alternative splicing.
Markus
M Andrea
MA
Basic & Clinical Genomics Laboratory, School of Medical Sciences and Bosch Institute, Building F13, The University of Sydney, NSW 2006, Australia.
Heinrich
Bettina
B
Raitskin
Oleg
O
Adams
David J
DJ
Mangs
Helena
H
Goy
Christine
C
Ladomery
Michael
M
Sperling
Ruth
R
Stamm
Stefan
S
Morris
Brian J
BJ
D017398:Alternative Splicing / Q000502:physiology*; D002460:Cell Line; D006367:HeLa Cells; D006801:Humans; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D022821:RNA Splice Sites; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017381:Spliceosomes / Q000378:metabolism; D025721:WT1 Proteins / Q000235:genetics / Q000378:metabolism*
D020033:Protein Isoforms; C473692:RBM4 protein, human; D022821:RNA Splice Sites; D016601:RNA-Binding Proteins; D025721:WT1 Proteins