Alternative splicing and disease mutations in protein interaction networks
01/04/2014 - Room Garden Room at 14:00 - External Seminar
Alternative splicing has been an essential mechanism in the evolution of protein functional diversity. The most common splicing event is alternative inclusion of complete exons, which often occurs in a tissue-specific manner. This hence raises the question of if, and how, such exons contribute to tissue identity. To address this, we compared the structural, functional and interaction properties of human tissue-specific protein segments to those of protein segments encoded by other alternative and by constitutive exons. We find that tissue-specific segments are highly enriched in features that indicate their role in mediating protein interactions. Furthermore, genes containing these exons tend to occupy central positions in interaction networks and include many signaling, developmental and disease genes. Alternative inclusion of such protein segments can therefore rewire interaction networks and signaling pathways in a tissue-specific manner. In this talk, I will also discuss another class of alternative exons, mutually exclusive exons, which tend to encode the same segment of a protein structure and fine-tune the protein function depending on the context. Finally, I will present the ongoing work on different roles of disease mutations in interaction networks.