Exploring the co-regulatory network between RNA binding proteins and miRNAs
We study the functional relationships between RNA binding proteins (RBPs) and microRNAs. Our recent analysis revealed a high percentage of shared microRNA targets among different RBPs. Among the shared targets of eight RBPs we observed an unexpected high number of microRNAs that are significantly enriched in specific cellular processes. To further explore the relationship between RBPs and the microRNA targets we constructed a co-regulatory networks between RBPs and microRNA, relaying on experimental validated regulatory interactions between RBPs and target microRNAs (CLIP) and between microRNAs and their targets (CLASH). The RBP-microRNA interaction network revealed interesting co-regulatory circuits between RBPs and microRNAs. Overall, our results suggest a tight regulation between specific RBPs and microRNAs.
(A). A schematic representation of a co-regulatory network between RNA-Binding Proteins (RBPs) and microRNAs (miRNSs). RBP-miRNA coregulatory networks were constructed for 666 different RBP pairs in HEK293 cells. Red and yellow circles represent the RBPs. Blue diamonds are pre-miRNA cliques that can are regulated by RBPs (black arrows). Green rectangles are protein-coding genes, targeted by miRNAs (red arrows) and/or RBPs (black arrows). (B). Significant network modules identified in the co-regulatory networks. The percentage of RBPs pairs that exhibit a significant network module are shown in the histogram. The topology of the enriched module is presented at the top of the corresponding bar.