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

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

Authors

M. Andrea Markus

Bettina Heinrich

Oleg Raitskin

David J. Adams

Helena Mangs

Christine Goy

Ruth Sperling

Stefan Stamm

Brian J. Morris



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. © 2006 Elsevier Inc. All rights reserved.

Citation

Markus, M. A., Heinrich, B., Raitskin, O., Adams, D. J., Mangs, H., Goy, C., …Morris, B. J. (2006). WT1 interacts with the splicing protein RBM4 and regulates its ability to modulate alternative splicing in vivo. Experimental Cell Research, 312(17), 3379-3388. https://doi.org/10.1016/j.yexcr.2006.07.008

Journal Article Type Article
Publication Date Oct 15, 2006
Journal Experimental Cell Research
Print ISSN 0014-4827
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 312
Issue 17
Pages 3379-3388
DOI https://doi.org/10.1016/j.yexcr.2006.07.008
Keywords alternative splicing, RNA binding proteins, speckles, Wilm's tumor suppressor, supraspliceosome
Public URL https://uwe-repository.worktribe.com/output/1036054
Publisher URL http://dx.doi.org/10.1016/j.yexcr.2006.07.008