The Architecture of the Human RNA-Binding Protein Regulatory Network

RNA-binding proteins (RBPs) are key players of post-transcriptional regulation of gene expression, relying on competitive and cooperative interactions to fine-tune their action. Several studies have described individual interactions of RBPs with RBP mRNAs. Here we present a systematic network investigation of fifty thousand interactions between RBPs and the UTRs of RBP mRNAs. We identified two structural features in this network. RBP clusters are groups of densely interconnected RBPs co-binding their targets, suggesting a tight control of cooperative and competitive behaviors. RBP chains are hierarchical structures connecting RBP clusters and driven by evolutionarily ancient RBPs. These features suggest that RBP chains may coordinate the different cell programs controlled by RBP clusters. Under this model, the regulatory signal flows through chains from one cluster to another, implementing elaborate regulatory plans. This work thus suggests RBP-RBP interactions as a backbone driving post-transcriptional regulation of gene expression to control RBPs action on their targets.