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An apparent pseudo-exon acts both as an alternative exon that leads to nonsense-mediated decay and as a zero-length exon

Lookup NU author(s): Dr Sushma Grellscheid

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Abstract

Pseudo-exons are intronic sequences that are flanked by apparent consensus splice sites but that are not observed in spliced mRNAs. Pseudo-exons are often difficult to activate by mutation and have typically been viewed as a conceptual challenge to our understanding of how the spliceosome discriminates between authentic and cryptic splice sites. We have analyzed an apparent pseudo-exon located downstream of mutually exclusive exons 2 and 3 of the rat α-tropomyosin (TM) gene. The TM pseudo-exon is conserved among mammals and has a conserved profile of predicted splicing enhancers and silencers that is more typical of a genuine exon than a pseudo-exon. Splicing of the pseudo-exon is fully activated for splicing to exon 3 by a number of simple mutations. Splicing of the pseudo-exon to exon 3 is predicted to lead to nonsense-mediated decay (NMD). In contrast, when "prespliced" to exon 2 it follows a "zero length exon" splicing pathway in which a newly generated 5′ splice site at the junction with exon 2 is spliced to exon 4. We propose that a subset of apparent pseudo-exons, as exemplified here, are actually authentic alternative exons whose inclusion leads to NMD. Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Publication metadata

Author(s): Grellscheid S-N, Smith CWJ

Publication type: Article

Publication status: Published

Journal: Molecular and Cellular Biology

Year: 2006

Volume: 26

Issue: 6

Pages: 2237-2246

ISSN (print): 0270-7306

ISSN (electronic): 1067-8824

Publisher: American Society for Microbiology

URL: http://dx.doi.org/10.1128/MCB.26.6.2237-2246.2006

DOI: 10.1128/MCB.26.6.2237-2246.2006

PubMed id: 16508000

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