RNA Structure Drives Interaction with Proteins
ARTICLE https://doi.org/10.1038/s41467-019-10923-5 OPEN RNA structure drives interaction with proteins Natalia Sanchez de Groot 1,8, Alexandros Armaos1,8, Ricardo Graña-Montes1,7, Marion Alriquet2,3, Giulia Calloni2,3, R. Martin Vabulas2,3 & Gian Gaetano Tartaglia1,4,5,6 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 net- works are not well understood. Here we investigated the relationship between the structure 1234567890():,; 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 com- position of a protein aggregate. We report that the tendency of proteins to phase-separate is reduced by interactions with specific RNAs. 1 Centre for Genomic Regulation (CRG), The Barcelona Institute for Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain. 2 Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt, 60438 Frankfurt am Main, Germany. 3 Institute of Biophysical Chemistry, Goethe University Frankfurt, 60438 Frankfurt am Main, Germany. 4 ICREA 23 Passeig Lluis Companys 08010 and Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.
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