WT1 interacts with the splicing protein RBM4 and regulates its ability to modulate alternative splicing in vivo
- Basic and Clinical Genomics Laboratory, School of Medical Sciences and Bosch Institute, Building F13, University of Sydney, NSW 2006 (Australia)
- Institute of Biochemistry, University of Erlangen, 91054 Erlangen (Germany)
- Department of Genetics, Hebrew University of Jerusalem, Jerusalem 91904 (Israel)
- Centre for Research in Biomedicine, Bristol Genomics Research Institute, Faculty of Applied Sciences, University of the West of England, Coldharbour Lane, Bristol BS16 1QY (United Kingdom)
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.
- OSTI ID:
- 20858041
- Journal Information:
- Experimental Cell Research, Vol. 312, Issue 17; Other Information: DOI: 10.1016/j.yexcr.2006.07.008; PII: S0014-4827(06)00283-7; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
- Country of Publication:
- United States
- Language:
- English
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