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RNA (2004), 10:1005-1018. Published by Cold Spring Harbor Laboratory Press. Copyright © 2004 RNA Society

BIOINFORMATICS

Computational comparative analyses of alternative splicing regulation using full-length cDNA of various eukaryotes

HITOMI ITOH1,2, TAKANORI WASHIO1,3 and MASARU TOMITA1,2

1 Laboratory for Bioinformatics, Institute for Advanced Biosciences, Keio University, Fujisawa, Kanagawa 252-8520, Japan
2 Department of Environmental Information, Keio University, Fujisawa, Kanagawa 252-8520, Japan

Reprint requests to: Takanori Washio, Laboratory for Bioinformatics, Institute for Advanced Biosciences, Keio University, Fujisawa, Kanagawa 252-8520, Japan; e-mail: washy{at}sfc.keio.ac.jp; fax: +81 (466) 47-5099.

We previously reported a computational approach to infer alternative splicing patterns from Mus musculus full-length cDNA clones and microarray data. Although we predicted a large number of unreported splice variants, the general mechanisms regulating alternative splicing were yet unknown. In the present study, we compared alternative exons and constitutive exons in terms of splice-site strength and frequency of potential regulatory sequences. These regulatory features were further compared among five different species: Homo sapiens, M. musculus, Arabidopsis thaliana, Oryza sativa, and Drosophila melanogaster. Solid statistical validations of our comparative analyses indicated that alternative exons have (1) weaker splice sites and (2) more potential regulatory sequences than constitutive exons. Based on our observations, we propose a combinatorial model of alternative splicing mechanisms, which suggests that alternative exons contain weak splice sites regulated alternatively by potential regulatory sequences on the exons.

Keywords: alternative splicing; exonic splicing enhancers; ESEs; splice-site strength


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