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

M. Andrea Markus, Bettina Heinrich, Oleg Raitskin, David J. Adams, Helena Mangs, Christine Goy, Michael Ladomery, Ruth Sperling, Stefan Stamm, Brian J. Morris

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

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.

Original languageEnglish
Pages (from-to)3379-3388
Number of pages10
JournalExperimental Cell Research
Volume312
Issue number17
DOIs
StatePublished - Oct 15 2006

Bibliographical note

Funding Information:
This work was supported by a grant from the Australian Research Council (to B.J.M.), The University of Sydney Cancer Research Fund (to M.A.M.), the Families of Spinal Muscular Atrophy (to S.S.), and the Association for International Cancer Research, U.K. (to M.L.). We thank Profs. N. Hastie, R. Davies and M. Niksic, MRC, Edinburgh, U.K. for providing us with pACT-plasmids.

Keywords

  • Alternative splicing
  • RNA binding proteins
  • Speckles
  • Supraspliceosome
  • Wilm's tumor suppressor

ASJC Scopus subject areas

  • Cell Biology

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