TY - JOUR
T1 - WT1 interacts with the splicing protein RBM4 and regulates its ability to modulate alternative splicing in vivo
AU - Markus, M. Andrea
AU - Heinrich, Bettina
AU - Raitskin, Oleg
AU - Adams, David J.
AU - Mangs, Helena
AU - Goy, Christine
AU - Ladomery, Michael
AU - Sperling, Ruth
AU - Stamm, Stefan
AU - Morris, Brian J.
PY - 2006/10/15
Y1 - 2006/10/15
N2 - 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.
AB - 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.
KW - Alternative splicing
KW - RNA binding proteins
KW - Speckles
KW - Supraspliceosome
KW - Wilm's tumor suppressor
UR - http://www.scopus.com/inward/record.url?scp=33748603768&partnerID=8YFLogxK
U2 - 10.1016/j.yexcr.2006.07.008
DO - 10.1016/j.yexcr.2006.07.008
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C2 - 16934801
AN - SCOPUS:33748603768
SN - 0014-4827
VL - 312
SP - 3379
EP - 3388
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 17
ER -
