A resource of RNA-binding protein motifs across eukaryotes reveals evolutionary dynamics and gene-regulatory function

RNA-binding proteins (RBPs) are key regulators of gene expression; however, their RNA-binding specificities, that is, motifs, have not been comprehensively determined. Here we introduce Eukaryotic Protein-RNA Interactions (EuPRI), a freely available resource of RNA motifs for 34,746 RBPs from 690 eukaryotes. EuPRI includes in vitro binding data for 504 RBPs, including newly collected RNAcompete data for 174 RBPs, along with thousands of predicted motifs. We predict these motifs with an algorithm, Joint Protein-Ligand Embedding, which can detect distant homology relationships and map specificity-determining peptides. EuPRI quadruples the number of available RBP motifs, expanding the motif repertoire across all major eukaryotic clades and assigning motifs to the majority of human RBPs. We demonstrate the utility of EuPRI for inferring post-transcriptional function and evolutionary relationships by identifying rapid, recent evolution of post-transcriptional regulatory networks in worms and plants, in contrast to the vertebrate RNA motif set, which has remained relatively stable after a large expansion between the metazoan and vertebrate ancestors.