title: WT1 interacts with the splicing protein RBM4 and regulates its ability to modulate alternative splicing in vivo.
abstract: 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.
authors.affiliation: Basic & Clinical Genomics Laboratory, School of Medical Sciences and Bosch Institute, Building F13, The University of Sydney, NSW 2006, Australia.
authors.forename: M Andrea
authors.initials: MA
authors.lastname: Markus
authors.forename: Bettina
authors.initials: B
authors.lastname: Heinrich
authors.forename: Oleg
authors.initials: O
authors.lastname: Raitskin
authors.forename: David J
authors.initials: DJ
authors.lastname: Adams
authors.forename: Helena
authors.initials: H
authors.lastname: Mangs
authors.forename: Christine
authors.initials: C
authors.lastname: Goy
authors.forename: Michael
authors.initials: M
authors.lastname: Ladomery
authors.forename: Ruth
authors.initials: R
authors.lastname: Sperling
authors.forename: Stefan
authors.initials: S
authors.lastname: Stamm
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Morris
mesh_terms: 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*
chemical_list: D020033:Protein Isoforms; C473692:RBM4 protein, human; D022821:RNA Splice Sites; D016601:RNA-Binding Proteins; D025721:WT1 Proteins