Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)The network structure of biological systems provides information on the underlying processes shaping their organization and dynamics. Here we examined the structure of the network depicting protein interactions within the spliceosome, the macromolecular complex responsible for splicing in eukaryotic cells. We show the interactions of less connected spliceosome proteins are nested subsets of the connections of the highly connected proteins. At the same time, the network has a modular structure with groups of proteins sharing similar interaction patterns. We then investigated the role of affinity and specificity in shaping the spliceosome network by adapting a probabilistic model originally designed to reproduce food webs. This food-web model was as successful in reproducing the structure of protein interactions as it is in reproducing interactions among species. The good performance of the model suggests affinity and specificity, partially determined by protein size and the timing of association to the complex, may be determining network structure. Moreover, because network models allow building ensembles of realistic networks while encompassing uncertainty they can be useful to examine the dynamics and vulnerability of intracelullar processes. Unraveling the mechanisms organizing the spliceosome interactions is important to characterize the role of individual proteins on splicing catalysis and regulation.5 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Killam TrustsFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPESP [2009/54567-6, 2009/54422-8, 2013/02738-7]CNPq [202581/2011-0]