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

doi:10.1016/j.yexcr.2006.07.008

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

Producción científica: Article › revisión exhaustiva

44 Citas (Scopus)

Resumen

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.

Idioma original	English
Páginas (desde-hasta)	3379-3388
Número de páginas	10
Publicación	Experimental Cell Research
Volumen	312
N.º	17
DOI	https://doi.org/10.1016/j.yexcr.2006.07.008
Estado	Published - oct 15 2006

Nota bibliográfica

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.

Financiación

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.

Financiadores
Families of Spinal Muscular Atrophy
Association for International Cancer Research
Australian Research Council
University of Technology at Sydney

ODS de las Naciones Unidas

Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

Good health and well being

ASJC Scopus subject areas

Cell Biology

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10.1016/j.yexcr.2006.07.008

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

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.",

keywords = "Alternative splicing, RNA binding proteins, Speckles, Supraspliceosome, Wilm's tumor suppressor",

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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.",

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AU - Markus, M. Andrea

AU - Heinrich, Bettina

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AU - Mangs, Helena

AU - Goy, Christine

AU - Ladomery, Michael

AU - Sperling, Ruth

AU - Stamm, Stefan

AU - Morris, Brian J.

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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

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DO - 10.1016/j.yexcr.2006.07.008

M3 - Article

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JO - Experimental Cell Research

JF - Experimental Cell Research

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

Resumen

Nota bibliográfica

Financiación

ODS de las Naciones Unidas

ASJC Scopus subject areas

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