Tissue-Specific Splicing of Disordered Segments that Embed Binding Motifs Rewires Protein Interaction Networks

Marija Buljan, Guilhem Chalancon, Sebastian Eustermann, Gunter P. Wagner, Monika Fuxreiter, Alex Bateman, M. Madan Babu

Research output: Contribution to journalArticle

225 Citations (Scopus)

Abstract

Alternative inclusion of exons increases the functional diversity of proteins. Among alternatively spliced exons, tissue-specific exons play a critical role in maintaining tissue identity. This raises the question of how tissue-specific protein-coding exons influence protein function. Here we investigate the structural, functional, interaction, and evolutionary properties of constitutive, tissue-specific, and other alternative exons in human. We find that tissue-specific protein segments often contain disordered regions, are enriched in posttranslational modification sites, and frequently embed conserved binding motifs. Furthermore, genes containing tissue-specific exons tend to occupy central positions in interaction networks and display distinct interaction partners in the respective tissues, and are enriched in signaling, development, and disease genes. Based on these findings, we propose that tissue-specific inclusion of disordered segments that contain binding motifs rewires interaction networks and signaling pathways. In this way, tissue-specific splicing may contribute to functional versatility of proteins and increases the diversity of interaction networks across tissues.

Original languageEnglish
Pages (from-to)871-883
Number of pages13
JournalMolecular Cell
Volume46
Issue number6
DOIs
Publication statusPublished - Jun 29 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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