Creation and disruption of protein features by alternative splicing - a novel mechanism to modulate function

Michael Hiller¹ , Klaus Huse², Matthias Platzer² and Rolf Backofen¹

¹Institute of Computer Science, Friedrich-Schiller-University Jena, Chair for Bioinformatics, Ernst-Abbe-Platz 2, 07743 Jena, Germany

²Genome Analysis, Institute of Molecular Biotechnology, Beutenbergstrasse 11, 07745 Jena, Germany

author email corresponding author email

Genome Biology 2005, 6:R58doi:10.1186/gb-2005-6-7-r58


Published:	22 June 2005

Subject areas: Molecular biology, Genome studies, Bioinformatics

Abstract

Background

Alternative splicing often occurs in the coding sequence and alters protein structure and function. It is mainly carried out in two ways: by skipping exons that encode a certain protein feature and by introducing a frameshift that changes the downstream protein sequence. These mechanisms are widespread and well investigated.

Results

Here, we propose an additional mechanism of alternative splicing to modulate protein function. This mechanism creates a protein feature by putting together two non-consecutive exons or destroys a feature by inserting an exon in its body. In contrast to other mechanisms, the individual parts of the feature are present in both splice variants but the feature is only functional in the splice form where both parts are merged. We provide evidence for this mechanism by performing a genome-wide search with four protein features: transmembrane helices, phosphorylation and glycosylation sites, and Pfam domains.

Conclusion

We describe a novel type of event that creates or removes a protein feature by alternative splicing. Current data suggest that these events are rare. Besides the four features investigated here, this mechanism is conceivable for many other protein features, especially for small linear protein motifs. It is important for the characterization of functional differences of two splice forms and should be considered in genome-wide annotation efforts. Furthermore, it offers a novel strategy for ab initio prediction of alternative splice events.