RNA structure drives interaction with proteins

The combination of high-throughput sequencing and in vivo crosslinking approaches leads to the progressive uncovering of the complex interdependence between cellular transcriptome and proteome. Yet, the molecular determinants governing interactions in protein-RNA networks are not well understood. Here we investigated the relationship between the structure of an RNA and its ability to interact with proteins. Analysing in silico, in vitro and in vivo experiments, we find that the amount of double-stranded regions in an RNA correlates with the number of protein contacts. This relationship -which we call structure-driven protein interactivity- allows classification of RNA types, plays a role in gene regulation and could have implications for the formation of phase-separated ribonucleoprotein assemblies. We validate our hypothesis by showing that a highly structured RNA can rearrange the composition of a protein aggregate. We report that the tendency of proteins to phase-separate is reduced by interactions with specific RNAs.The research leading to these results has been supported by European Research Council (RIBOMYLOME_309545 to G.G.T. and METAMETA_311522 to R.M.V.), Spanish Ministry of Economy and Competitiveness (BFU2014-55054-P and BFU2017-86970-P), ‘Fundació La Marató de TV3’ (PI043296) and the collaboration with Peter St. George-Hyslop financed by the Wellcome Trust. We acknowledge support of the Spanish Ministry of Economy and Competitiveness, ‘Centro de Excelencia Severo Ochoa 2013-2017’. We also acknowledge the support of the CERCA Programme/Generalitat de Catalunya and of Spanish Ministry for Science and Competitiveness (MINECO) to the EMBL partnership