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BMC Genomics. 2013 Jun 7;14:379. doi: 10.1186/1471-2164-14-379.

Alternative splicing tends to avoid partial removals of protein-protein interaction sites.

Author information

  • 1Centre for Molecular Bioinformatics, Department of Biology, University of Rome Tor Vergata, Rome, Italy.

Abstract

BACKGROUND:

Anecdotal evidence of the involvement of alternative splicing (AS) in the regulation of protein-protein interactions has been reported by several studies. AS events have been shown to significantly occur in regions where a protein interaction domain or a short linear motif is present. Several AS variants show partial or complete loss of interface residues, suggesting that AS can play a major role in the interaction regulation by selectively targeting the protein binding sites. In the present study we performed a statistical analysis of the alternative splicing of a non-redundant dataset of human protein-protein interfaces known at molecular level to determine the importance of this way of modulation of protein-protein interactions through AS.

RESULTS:

Using a Cochran-Mantel-Haenszel chi-square test we demonstrated that the alternative splicing-mediated partial removal of both heterodimeric and homodimeric binding sites occurs at lower frequencies than expected, and this holds true even if we consider only those isoforms whose sequence is less different from that of the canonical protein and which therefore allow to selectively regulate functional regions of the protein. On the other hand, large removals of the binding site are not significantly prevented, possibly because they are associated to drastic structural changes of the protein. The observed protection of the binding sites from AS is not preferentially directed towards putative hot spot interface residues, and is widespread to all protein functional classes.

CONCLUSIONS:

Our findings indicate that protein-protein binding sites are generally protected from alternative splicing-mediated partial removals. However, some cases in which the binding site is selectively removed exist, and here we discuss one of them.

PMID:
23758645
[PubMed - indexed for MEDLINE]
PMCID:
PMC3700808
Free PMC Article
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