Effect of alternative splicing on the degree centrality of nodes in protein-protein interaction networks of Homo sapiens

Abstract

Alternative splicing of an mRNA transcript could lead to formation of protein products having a different number of binding/interacting domains which in turn may relate to the number of physical interactions they make with other proteins and hence a node in a protein-protein interaction network can be considered as an ensemble of its splice variants and its degree (i.e., number of physical interactions it makes with other nodes) as the union of the individual degrees of its splice variants. In this communication, we demonstrate that in the eukaryotic protein-protein interaction networks hubs tend to have a significantly higher number of splice variants than nonhubs. Also, hubs have a distinct frequency distribution of splice variants as compared to nonhubs. Furthermore, nodes with high number of splice variants, in general, are associated with high structural disorderedness. We also show that the degree of a node is substantially contributed by its structurally disordered splice variants. This suggests that the propensity of a node for a large number of interactions arises as a consequence of structurally disordered splice variants. Our work, therefore, sheds light on the phenomenon of alternative splicing as a significant contributor toward the "connection diversity" of nodes in a eukaryotic PPI network and hence to its functionality. © 2013 American Chemical Society.