Large-scale map of RNA binding protein interactomes across the mRNA life-cycle (Street, Rothamel, and Brannan et al., 2024)

While substantial effort has assigned RBPs to RNA substrates, less exploration has leveraged protein-protein interactions (PPIs) to study proteins in mRNA life-cycle stages. We generated an RNA-aware RBP-centric PPI map across the mRNA life-cycle by immunopurification-mass spectrometry of ~100 endogenous RBPs in the presence or absence of RNase, augmented by size exclusion chromatography-mass spectrometry.

We identify 8,742 known and 20,802 novel interactions between 1125 proteins and determine that 73% of IP interactions are RNA-regulated. Our interactome links proteins, many of unknown function, with distinct life-cycle stages, linking nearly half the proteins to multiple stages. We demonstrate the value of this resource by assigning novel functions to the two most connected proteins.