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Nucleic Acids Research 2005 33(17):5574-5582; doi:10.1093/nar/gki858
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Published online 28 September 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions{at}oxfordjournals.org

Article

The importance of being divisible by three in alternative splicing

Alon Magen and Gil Ast*

Department of Human Genetics and Molecular Medicine, Sackler Faculty of Medicine, Tel Aviv University Ramat Aviv 69978, Israel

*To whom correspondence should be addressed. Tel: +972 3 640 6893; Fax +972 3 640 9900; Email: gilast{at}post.tau.ac.il

Received May 22, 2005. Revised August 10, 2005. Accepted September 7, 2005.

Alternative splicing events that are conserved in orthologous genes in different species are commonly viewed as reliable evidence of authentic, functionally significant alternative splicing events. Several recent bioinformatic analyses have shown that conserved alternative exons possess several features that distinguish them from alternative exons that are species-specific. One of the most striking differences between conserved and species-specific alternative exons is the high percentage of exons that preserve the reading frame (exons whose length is an exact multiple of 3, termed symmetrical exons) among the conserved alternative exons. Here, we examined conserved alternative exons and found several features that differentiate between symmetrical and non-symmetrical alternative exons. We show that symmetrical alternative exons have a strong tendency not to disrupt protein domain structures, whereas the tendency of non-symmetrical alternative exons to overlap with different fractions of protein domains is similar to that of constitutive exons. Additionally, skipping isoforms of non-symmetrical alternative exons are strongly underrepresented, compared with their including isoforms, suggesting that skipping of a large fraction of non-symmetrical alternative exons produces transcripts that are degraded by the nonsense-mediated mRNA decay mechanism. Non-symmetrical alternative exons also show a tendency to reside in the 5' half of the CDS. These findings suggest that alternative splicing of symmetrical and non-symmetrical exons is governed by different selective pressures and serves different purposes.


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