Sanchez de Groot, NataliaArmaos, Alexandros, 1989-Graña-Montes, RicardoAlriquet, MarionCalloni, GiuliaVabulas, R. MartinTartaglia, Gian Gaetano2019-09-302019-09-302019Sanchez de Groot N, Armaos A, Graña-Montes R, Alriquet M, Calloni G, Vabulas RM et al. RNA structure drives interaction with proteins. Nat Commun. 2019;10(1):3246. DOI: 10.1038/s41467-019-10923-52041-1723http://hdl.handle.net/10230/42357The 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.application/pdfeng© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41467-019-10923-5Computational biology and bioinformaticsRNATranscriptomicsinfo:eu-repo/semantics/openAccess