Abstract
BackgroundGene regulatory networks control the global gene expression and the dynamics of protein output in living cells. In multicellular organisms, transcription factors and microRNAs are the major families of gene regulators. Recent studies have suggested that these two kinds of regulators share similar regulatory logics and participate in cooperative activities in the gene regulatory network; however, their combinational regulatory effects and preferences on the protein interaction network remain unclear.MethodsIn this study, we constructed a global human gene regulatory network comprising both transcriptional and post-transcriptional regulatory relationships, and integrated the protein interactome into this network. We then screened the integrated network for four types of regulatory motifs: single-regulation, co-regulation, crosstalk, and independent, and investigated their topological properties in the protein interaction network.ResultsAmong the four types of network motifs, the crosstalk was found to have the most enriched protein-protein interactions in their downstream regulatory targets. The topological properties of these motifs also revealed that they target crucial proteins in the protein interaction network and may serve important roles of biological functions.ConclusionsAltogether, these results reveal the combinatorial regulatory patterns of transcription factors and microRNAs on the protein interactome, and provide further evidence to suggest the connection between gene regulatory network and protein interaction network.
Highlights
Gene regulatory networks control the global gene expression and the dynamics of protein output in living cells
We collected 144,490 post-transcriptional regulatory relationships between 153 miRNA families and 11,161 target genes with conserved binding sites of corresponding miRNAs. These regulatory relationships collected from the three databases were merged together to construct our global gene regulatory network (GRN), in which nodes represent regulators (TFs/miRNAs) or target genes/proteins, and edges represent the regulatory relationships between regulators and targets
Gene regulatory network properties In order to provide a global view of human GRN, both transcriptional and post-transcriptional regulations were analyzed jointly and respectively in this study
Summary
Gene regulatory networks control the global gene expression and the dynamics of protein output in living cells. Previous studies [17,18,19,20] investigating the co-regulation between miRNAs and TFs found a variety of significant network motifs overrepresented in the co-regulation network, suggesting that the gene regulatory system requires close cooperation between transcriptional and post-transcriptional layers. These studies each proposed that the network motifs might be used as building blocks in GRNs. In order to understand how these motifs in the GRN influence the downstream biological processes, further studies on the protein interactome are essential
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