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Nucleic Acids Research Advance Access originally published online on February 14, 2008
Nucleic Acids Research 2008 36(6):2012-2023; doi:10.1093/nar/gkn024
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Nucleic Acids Research, 2008, Vol. 36, No. 6 2012-2023
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Molecular Biology

Alternative splicing of Alu exons—two arms are better than one

Nurit Gal-Mark, Schraga Schwartz and Gil Ast*

Department of Human Genetics and Molecular Biochemistry, 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 September 24, 2007. Revised January 16, 2008. Accepted January 16, 2008.

Alus, primate-specific retroelements, are the most abundant repetitive elements in the human genome. They are composed of two related but distinct monomers, left and right arms. Intronic Alu elements may acquire mutations that generate functional splice sites, a process called exonization. Most exonizations occur in right arms of antisense Alu elements, and are alternatively spliced. Here we show that without the left arm, exonization of the right arm shifts from alternative to constitutive splicing. This eliminates the evolutionary conserved isoform and may thus be selected against. We further show that insertion of the left arm downstream of a constitutively spliced non-Alu exon shifts splicing from constitutive to alternative. Although the two arms are highly similar, the left arm is characterized by weaker splicing signals and lower exonic splicing regulatory (ESR) densities. Mutations that improve these potential splice signals activate exonization and shift splicing from the right to the left arm. Collaboration between two or more putative splice signals renders the intronic left arm with a pseudo-exon function. Thus, the dimeric form of the Alu element fortuitously provides it with an evolutionary advantage, allowing enrichment of the primate transcriptome without compromising its original repertoire.


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