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 language | English |
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Pages (from-to) | 3379-3388 |
Number of pages | 10 |
Journal | Experimental Cell Research |
Volume | 312 |
Issue number | 17 |
DOIs | |
State | Published - 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