The architecture of the human RNA-binding protein regulatory network

RNA-binding proteins (RBPs) are key players in post-transcriptional regulation of gene expression, implicated in both cellular physiology and pathology. Several studies have described individual interactions of RBP proteins with RBP mRNAs, evocative of an RBP regulatory hierarchy. Here we present the first systematic investigation of this hierarchy, based on a network including twenty thousand experimentally determined interactions between RBPs and bound RBP mRNAs. RBPs bind their mRNA in half of the cases, providing conclusive evidence of their general propensity to autoregulation. The RBP regulatory network is dominated by directional chains, rather than by modular communities as in the transcription factor regulatory network. These chains are initiated by an essential class of RBPs, the iRBPs. One of these, RBMX, initiates several thousand chains reaching most human RBPs. Our results show that chains make the network hierarchical, forming a post-transcriptional backbone that allows the fine-grained control of RBPs and their targets.