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Nucleic Acids Research 2006 34(1):23-31; doi:10.1093/nar/gkj408
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Published online 3 January 2006

© The Author 2006. 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

Alternative splicing regulation at tandem 3' splice sites

Martin Akerman and Yael Mandel-Gutfreund*

Department of Biology, Technion-Institute of Technology Haifa 32000, Israel

*To whom correspondence should be addressed. Tel: +972 4 8293958; Fax: +972 4 8225153; Email: yaelmg{at}tx.technion.ac.il

Received October 17, 2005. Revised December 6, 2005. Accepted December 6, 2005.

Alternative splicing (AS) constitutes a major mechanism creating protein diversity in humans. Previous bioinformatics studies based on expressed sequence tag and mRNA data have identified many AS events that are conserved between humans and mice. Of these events, ~25% are related to alternative choices of 3' and 5' splice sites. Surprisingly, half of all these events involve 3' splice sites that are exactly 3 nt apart. These tandem 3' splice sites result from the presence of the NAGNAG motif at the acceptor splice site, recently reported to be widely spread in the human genome. Although the NAGNAG motif is common in human genes, only a small subset of sites with this motif is confirmed to be involved in AS. We examined the NAGNAG motifs and observed specific features such as high sequence conservation of the motif, high conservation of ~30 bp at the intronic regions flanking the 3' splice site and overabundance of cis-regulatory elements, which are characteristic of alternatively spliced tandem acceptor sites and can distinguish them from the constitutive sites in which the proximal NAG splice site is selected. Our findings imply that AS at tandem splice sites and constitutive splicing of the distal NAG are highly regulated.


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