Sinha Anupam, Nagarajaram Hampapathalu Adimurthy
Laboratory of Computational Biology, Centre for DNA Fingerprinting & Diagnostics (CDFD), Gruhakalpa, Nampally, Hyderabad 500001, Andhra Pradesh, India.
J Proteome Res. 2013 Apr 5;12(4):1980-8. doi: 10.1021/pr4000812. Epub 2013 Mar 13.
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.
mRNA转录本的可变剪接可导致形成具有不同数量结合/相互作用结构域的蛋白质产物，这反过来可能与它们与其他蛋白质发生物理相互作用的数量有关，因此蛋白质-蛋白质相互作用网络中的一个节点可被视为其剪接变体的集合，其度数（即与其他节点发生物理相互作用的数量）为其剪接变体各个度数的并集。在本通讯中，我们证明在真核生物蛋白质-蛋白质相互作用网络中，枢纽节点往往比非枢纽节点具有显著更多的剪接变体。此外，与非枢纽节点相比，枢纽节点具有独特的剪接变体频率分布。此外，一般来说，具有大量剪接变体的节点与高度的结构无序性相关。我们还表明，节点的度数在很大程度上由其结构无序的剪接变体所贡献。这表明节点具有大量相互作用的倾向是结构无序的剪接变体的结果。因此，我们的工作揭示了可变剪接现象作为真核生物PPI网络中节点“连接多样性”及其功能的重要贡献者的作用。
