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

被引:292
作者
Buljan, Marija [1 ,2 ]
Chalancon, Guilhem [1 ]
Eustermann, Sebastian [1 ]
Wagner, Gunter P. [3 ,4 ]
Fuxreiter, Monika [1 ,5 ]
Bateman, Alex [2 ]
Babu, M. Madan [1 ]
机构
[1] MRC Lab Mol Biol, Cambridge CB2 0QH, England
[2] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England
[3] Yale Univ, Yale Syst Biol Inst, West Haven, CT 06516 USA
[4] Yale Univ, Dept Ecol & Evolutionary Biol, West Haven, CT 06516 USA
[5] Univ Debrecen, Med & Hlth Sci Ctr, Dept Biochem & Mol Biol, H-4032 Debrecen, Hungary
基金
英国医学研究理事会; 英国惠康基金;
关键词
RNA SELECTION PRESSURE; INTRINSIC DISORDER; FUNCTIONAL DIVERSITY; EVOLUTION; CONSEQUENCES; PLURIPOTENCY; PROTEOMICS; MUTATIONS; ISOFORMS; GENOMES;
D O I
10.1016/j.molcel.2012.05.039
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:871 / 883
页数:13
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