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Originally published In Press as doi:10.1074/jbc.M011769200 on March 1, 2001
J. Biol. Chem., Vol. 276, Issue 20, 17597-17602, May 18, 2001
Dimethyl Sulfoxide Affects the Selection of Splice Sites*
Lucie
Bolduc ,
Benoit
Labrecque,
Mélanie
Cordeau,
Marco
Blanchette§, and
Benoit
Chabot¶
From the Département de Microbiologie et d'Infectiologie,
Faculté de Médecine, Université de Sherbrooke,
Sherbrooke, Québec, Canada J1H 5N4
Depending on the cell lines and cell types,
dimethyl sulfoxide (Me2SO) can induce or block
cell differentiation and apoptosis. Although Me2SO
treatment alters many levels of gene expression, the molecular
processes that are directly affected by Me2SO have not been
clearly identified. Here, we report that Me2SO affects splice site selection on model pre-mRNAs incubated in a nuclear extract prepared from HeLa cells. A shift toward the proximal pair of
splice sites was observed on pre-mRNAs carrying competing 5'-splice
sites or competing 3'-splice sites. Because the activity of recombinant
hnRNP A1 protein was similar when added to extracts containing or
lacking Me2SO, the activity of endogenous A1 proteins is
probably not affected by Me2SO. Notably, in a manner
reminiscent of SR proteins, Me2SO activated splicing in a
HeLa S100 extract. Moreover, the activity of recombinant SR proteins in
splice site selection in vitro was improved by
Me2SO. Polar solvents like DMF and formamide similarly
modulated splice site selection in vitro but formamide did
not activate a HeLa S100 extract. We propose that Me2SO
improves ionic interactions between splicing factors that contain
RS-domains. The direct impact of Me2SO on
alternative splicing may explain, at least in part, the different and
sometimes opposite effects of Me2SO on cell differentiation
and apoptosis.
*
This work was supported in part by a grant from the
National Cancer Institute of Canada with funds from the Canadian Cancer Society (to B. C.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Recipient of a studentship from the Fonds pour la Formation de
Chercheurs et l'Aide à la Recherche (FCAR).
§
Recipient of a studentship from the Medical Research Council of
Canada. Present Address: Dept. of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3204.
¶
Research Scholar from the Fond de la Recherche en Santé
du Québec and member of the Sherbrooke RNA/RNP group supported by the FCAR. To whom correspondence should be addressed. Tel.:
819-564-5295; Fax: 819-564-5392; E-mail:
b.chabot@courrier.usherb.ca.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.

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