Expression of the muscle-specific 2a isoform of the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2) requires activation of an inefficient optional splice process at the 3´ end of the primary gene transcript. The sequence elements required for this regulated splice event were studied by modifying a minigene containing the 3´ end of the SERCA2 gene. An important requirement appears to be a strong muscle-specific acceptor site, as replacing it by a weak one prevented the induction of muscle-type splicing during myogenic differentiation. The induction of muscle-type splicing did not depend on positive cis-active sequences in the muscle-specific exon. On the other hand, replacement of a broad region around the acceptor site dramatically deregulated the expression pattern, as this modification strongly induced muscle-type splicing in undifferentiated muscle cells and in fibroblasts. This cis-active region is also involved in the suppression of the neuronal type of splicing. Furthermore selective replacement of the acceptor site as well as deletions or replacements in the muscle-specific exon induced muscle-type splicing to various extents in undifferentiated myogenic cells. Therefore sequence elements in the distal part of the optional intron and in the muscle-specific exon contribute to the suppression of muscle-specific SERCA2 splicing.
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March 1997
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Research Article|
March 15 1997
Sequence elements surrounding the acceptor site suppress alternative splicing of the sarco/endoplasmic reticulum Ca2+-ATPase 2 gene transcript
Ludo VAN DEN BOSCH;
Ludo VAN DEN BOSCH
*
1Laboratory of Physiology, University of Leuven (KULeuven), Campus Gasthuisberg, B-3000 Leuven, Belgium
*To whom correspondence should be addressed.
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Luc MERTENS;
Luc MERTENS
1Laboratory of Physiology, University of Leuven (KULeuven), Campus Gasthuisberg, B-3000 Leuven, Belgium
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Sofie GIJSBERS;
Sofie GIJSBERS
1Laboratory of Physiology, University of Leuven (KULeuven), Campus Gasthuisberg, B-3000 Leuven, Belgium
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Mark VER HEYEN;
Mark VER HEYEN
1Laboratory of Physiology, University of Leuven (KULeuven), Campus Gasthuisberg, B-3000 Leuven, Belgium
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Frank WUYTACK;
Frank WUYTACK
1Laboratory of Physiology, University of Leuven (KULeuven), Campus Gasthuisberg, B-3000 Leuven, Belgium
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Jan EGGERMONT
Jan EGGERMONT
1Laboratory of Physiology, University of Leuven (KULeuven), Campus Gasthuisberg, B-3000 Leuven, Belgium
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Publisher: Portland Press Ltd
Received:
September 13 1996
Revision Received:
October 28 1996
Accepted:
October 29 1996
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1997
1997
Biochem J (1997) 322 (3): 885–891.
Article history
Received:
September 13 1996
Revision Received:
October 28 1996
Accepted:
October 29 1996
Citation
Ludo VAN DEN BOSCH, Luc MERTENS, Sofie GIJSBERS, Mark VER HEYEN, Frank WUYTACK, Jan EGGERMONT; Sequence elements surrounding the acceptor site suppress alternative splicing of the sarco/endoplasmic reticulum Ca2+-ATPase 2 gene transcript. Biochem J 15 March 1997; 322 (3): 885–891. doi: https://doi.org/10.1042/bj3220885
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