Updated project metadata. 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 S. cerevisiae, the number of proteins identified as RBPs has largely increased over the last decade. However, the cellular function for most of these novel RBPs still remains largely unexplored. We use mass spectrometry-based quantitative proteomics to systematically identify protein-protein interactions (PPIs), and RNA-dependent interactions (RDIs) to create a novel data set for 40 RBPs associated with the mRNA life cycle. Domain, functional, and pathway enrichment analysis revealed an overrepresentation of RNA functionalities among the enriched interactors. With the creation of extensive PPI and RDI networks, we revealed putative new members within RNA-associated pathways, as well as highlighted potential new roles of several RBPs, such as metabolism. 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.