Caspase-2 pre-mRNA alternative splicing: Identification of an intronic element containing a decoy 3′ acceptor site

Jocelyn Côté, Sophie Dupuis, Zhi Hong Jiang, Jane Y. Wu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

We have established a model system using the caspase-2 pre-mRNA and initiated a study on the role of alternative splicing in regulation of programmed cell death. A caspase-2 minigene construct has been made that can be alternatively spliced in transfected cells and in nuclear extracts. Using this system, we have identified a 100-nt region in downstream intron 9 that inhibits the inclusion of the 61-bp alternative exon. This element (In100) can facilitate exon skipping in the context of competing 3′ or 5′ splice sites, but not in single-intron splicing units. The In100 element is also active in certain heterologous pre-mRNAs, although in a highly context-dependent manner. Interestingly, we found that In100 contains a sequence that highly resembles a bona fide 3′ splice site. We provide evidence that this sequence acts as a "decoy" acceptor site that engages in U2 snRNP-dependent but nonproductive splicing complexes with the 5′ splice site of exon 9, hence conferring competitive advantage to the exon-skipping splicing event (E8-E10). These results reveal a mechanism of action for a negative intronic regulatory element and uncover a role for U2 snRNP in the regulation of alternative splicing.

Original languageEnglish (US)
Pages (from-to)938-943
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number3
DOIs
StatePublished - Jan 30 2001

ASJC Scopus subject areas

  • General

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