Caspase-2 Pre-mRNA Alternative Splicing: Identification of an Intronic Element Containing a Decoy 3' Acceptor Site

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2001 Feb 7

PMID 11158574

Citations 27

Authors

J Cote

S Dupuis

Z Jiang

J Y Wu

Affiliations

Soon will be listed here.

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.

Citing Articles

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SRSF9 Regulates Cassette Exon Splicing of Caspase-2 by Interacting with Its Downstream Exon.

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TCF3 mutually exclusive alternative splicing is controlled by long-range cooperative actions between hnRNPH1 and PTBP1.

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An important class of intron retention events in human erythroblasts is regulated by cryptic exons proposed to function as splicing decoys.

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