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Sequence elements surrounding the acceptor site suppress alternative splicing of the sarco/endoplasmic reticulum Ca2+-ATPase 2 gene transcript

1997; Portland Press; Volume: 322; Issue: 3 Linguagem: Inglês

10.1042/bj3220885

1470-8728

Ludo Van Den Bosch, Luc Mertens, Sofie Gijsbers, Mark Ver Heyen, Frank Wuytack, Jan Eggermont,

Endoplasmic Reticulum Stress and Disease

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.