title: Tissue-specific splicing of disordered segments that embed binding motifs rewires protein interaction networks.
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.
authors: MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK. mbuljan@mrc-lmb.cam.ac.uk
authors: Marija
authors: M
authors: Buljan
authors: Guilhem
authors: G
authors: Chalancon
authors: Sebastian
authors: S
authors: Eustermann
authors: Gunter P
authors: GP
authors: Wagner
authors: Monika
authors: M
authors: Fuxreiter
authors: Alex
authors: A
authors: Bateman
authors: M Madan
authors: MM
authors: Babu
mesh_terms: D017398:Alternative Splicing; D019143:Evolution, Molecular; D005091:Exons; D006801:Humans; D008954:Models, Biological; D009928:Organ Specificity; D060066:Protein Interaction Maps; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D012326:RNA Splicing; D013329:Structure-Activity Relationship
chemical_list: D011506:Proteins