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Nucleic Acids Research 2005 33(18):5904-5913; doi:10.1093/nar/gki893
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Published online 19 October 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

A genome-wide survey demonstrates widespread non-linear mRNA in expressed sequences from multiple species

Richard J. Dixon*, Ian C. Eperon1, Laurence Hall and Nilesh J. Samani

Department of Cardiovascular Sciences, University of Leicester, Clinical Sciences Wing, Glenfield Hospital Leicester LE3 9QP, UK 1Department of Biochemistry, University of Leicester, Clinical Sciences Wing, Glenfield Hospital Leicester LE3 9QP, UK

*To whom correspondence should be addressed. Tel: +44 116 250 2541; Fax: +44 116 287 5792; Email: rd67{at}le.ac.uk

Received August 22, 2005. Revised September 26, 2005. Accepted September 26, 2005.

We describe here the results of the first genome-wide survey of candidate exon repetition events in expressed sequences from human, mouse, rat, chicken, zebrafish and fly. Exon repetition is a rare event, reported in <10 genes, in which one or more exons is tandemly duplicated in mRNA but not in the gene. To identify candidates, we analysed database sequences for mRNA transcripts in which the order of the spliced exons does not follow the linear genomic order of the individual gene [events we term rearrangements or repetition in exon order (RREO)]. Using a computational approach, we have identified 245 genes in mammals that produce RREO events. RREO in mRNA occurs predominantly in the coding regions of genes. However, exon 1 is never involved. Analysis of the open reading frames suggests that this process may increase protein diversity and regulate protein expression via nonsense-mediated RNA decay. The sizes of the exons and introns involved around these events suggest a gene model structure that may facilitate non-linear splicing. These findings imply that RREO affects a significant subset of genes within a genome and suggests that non-linear information encoded within the genomes of complex organisms could contribute to phenotypic variation.


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