Matrix-screening reveals a vast potential for direct protein-protein interactions among RNA binding proteins

Benjamin Lang, Jae-Seong Yang, Mireia Garriga-Canut, Silvia Speroni, Moritz Aschern, Maria Gili, Tobias Hoffmann, Gian Gaetano Tartaglia, Sebastian P Maurer
2021 Nucleic Acids Research  
RNA-binding proteins (RBPs) are crucial factors of post-transcriptional gene regulation and their modes of action are intensely investigated. At the center of attention are RNA motifs that guide where RBPs bind. However, sequence motifs are often poor predictors of RBP-RNA interactions in vivo. It is hence believed that many RBPs recognize RNAs as complexes, to increase specificity and regulatory possibilities. To probe the potential for complex formation among RBPs, we assembled a library of
more » ... 8 mammalian RBPs and used rec-Y2H matrix screening to detect direct interactions between RBPs, sampling > 600 K interactions. We discovered 1994 new interactions and demonstrate that interacting RBPs bind RNAs adjacently in vivo. We further find that the mRNA binding region and motif preferences of RBPs deviate, depending on their adjacently binding interaction partners. Finally, we reveal novel RBP interaction networks among major RNA processing steps and show that splicing impairing RBP mutations observed in cancer rewire spliceosomal interaction networks. The dataset we provide will be a valuable resource for understanding the combinatorial interactions of RBPs with RNAs and the resulting regulatory outcomes.
doi:10.1093/nar/gkab490 pmid:34133714 fatcat:6lpemmmyzvfqpgijn4bzquo26a