RNA-dependent interactome allows network-based assignment of RNA-binding protein function.

RNA-binding proteins (RBPs) form highly diverse and dynamic ribonucleoprotein complexes, whose functions determine the molecular fate of the bound RNA. In the model organism Sacchromyces cerevisiae, the number of proteins identified as RBPs has greatly increased over the last decade. However, the cellular function of most of these novel RBPs remains largely unexplored. We used mass spectrometry-based quantitative proteomics to systematically identify protein-protein interactions (PPIs) and RNA-dependent interactions (RDIs) to create a novel dataset for 40 RBPs that are associated with the mRNA life cycle. Domain, functional and pathway enrichment analyses revealed an over-representation of RNA functionalities among the enriched interactors. Using our extensive PPI and RDI networks, we revealed putative new members of RNA-associated pathways, and highlighted potential new roles for several RBPs. Our RBP interactome resource is available through an online interactive platform as a community tool to guide further in-depth functional studies and RBP network analysis (https://www.butterlab.org/RINE).