Open Access Highly Accessed Research article

Alternative splicing and protein function

AD Neverov1, II Artamonova2, RN Nurtdinov3, D Frishman24, MS Gelfand135* and AA Mironov13

Author Affiliations

1 State Scientific Center GosNIIGenetika, 1st Dorozhny proezd 1, Moscow, 117545, Russia

2 Institute for Bioinformatics/MIPS, GSF – National Research Center for Environment and Health, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany

3 Department of Bioengineering and Bioinformatics, M.V.Lomonosov Moscow State University, Vorobievy Gory 1–73, Moscow, 119992, Russia

4 Department of Genome Oriented Bioinformatics, Technical University of Munich, Wissenschaftszentrum Weihenstephan, 85350 Freising, Germany

5 Institute for Information Transmission Problems RAS, Bolshoi Karetny pereulok 19, Moscow, 127994, Russia

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BMC Bioinformatics 2005, 6:266  doi:10.1186/1471-2105-6-266

Published: 7 November 2005

Abstract

Background

Alternative splicing is a major mechanism of generating protein diversity in higher eukaryotes. Although at least half, and probably more, of mammalian genes are alternatively spliced, it was not clear, whether the frequency of alternative splicing is the same in different functional categories. The problem is obscured by uneven coverage of genes by ESTs and a large number of artifacts in the EST data.

Results

We have developed a method that generates possible mRNA isoforms for human genes contained in the EDAS database, taking into account the effects of nonsense-mediated decay and translation initiation rules, and a procedure for offsetting the effects of uneven EST coverage. Then we computed the number of mRNA isoforms for genes from different functional categories. Genes encoding ribosomal proteins and genes in the category "Small GTPase-mediated signal transduction" tend to have fewer isoforms than the average, whereas the genes in the category "DNA replication and chromosome cycle" have more isoforms than the average. Genes encoding proteins involved in protein-protein interactions tend to be alternatively spliced more often than genes encoding non-interacting proteins, although there is no significant difference in the number of isoforms of alternatively spliced genes.

Conclusion

Filtering for functional isoforms satisfying biological constraints and accountung for uneven EST coverage allowed us to describe differences in alternative splicing of genes from different functional categories. The observations seem to be consistent with expectations based on current biological knowledge: less isoforms for ribosomal and signal transduction proteins, and more alternative splicing of interacting and cell cycle proteins.