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DNA Research Advance Access originally published online on February 14, 2008
DNA Research 2008 15(2):63-72; doi:10.1093/dnares/dsm036
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© The Author 2008. Kazusa DNA Research Institute
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@oxfordjournals.org

Computational Analysis of Full-length cDNAs Reveals Frequent Coupling Between Transcriptional and Splicing Programs

Tzu-Ming Chern, Nicodeme Paul, Erik van Nimwegen and Mihaela Zavolan*

Division of Bioinformatics, Biozentrum, University of Basel, Klingelbergstrasse 50-70, Basel CH-4056, Switzerland

Received 31 August 2007 ; accepted 25 December 2007.

High-throughput sequencing studies revealed that the majority of human and mouse multi-exon genes have multiple splice forms. High-density oligonucleotide array-based measurements have further established that many exons are expressed in a tissue-specific manner. The mechanisms underlying the tissue-dependent expression of most alternative exons remain, however, to be understood. In this study, we focus on one possible mechanism, namely the coupling of (tissue specific) transcription regulation with alternative splicing. We analyzed the FANTOM3 and H-Invitational datasets of full-length mouse and human cDNAs, respectively, and found that in transcription units with multiple start sites, the inclusion of at least 15% and possibly up to 30% of the ‘cassette’ exons correlates with the use of specific transcription start sites (TSS). The vast majority of TSS-associated exons are conserved between human and mouse, yet the conservation is weaker when compared with TSS-independent exons. Additionally, the currently available data only support a weak correlation between the probabilities of TSS association of orthologous exons. Our analysis thus suggests frequent coupling of transcriptional and splicing programs, and provides a large dataset of exons on which the molecular basis of this coupling can be further studied.

Key words: alternative splicing; transcription initiation

* To whom correspondence should be addressed. Tel. +41 61-267-1576. Fax. +41 61-267-1584. E-mail: mihaela.zavolan{at}unibas.ch

Edited by Osamu Ohara


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