Lorenzo Gotor, Maria de las NievesArmaos, Alexandros, 1989-Calloni, GiuliaTorrent Burgas, MarcVabulas, R. MartinSánchez de Groot, NataliaTartaglia, Gian Gaetano2020-10-302020-10-302020Lorenzo Gotor N, Armaos A, Calloni G, Torrent Burgas M, Vabulas RM, De Groot NS, Tartaglia GG. RNA-binding and prion domains: the Yin and Yang of phase separation. Nucleic Acids Res. 2020; 48(17):9491-504. DOI: 10.1093/nar/gkaa6810305-1048http://hdl.handle.net/10230/45622Proteins and RNAs assemble in membrane-less organelles that organize intracellular spaces and regulate biochemical reactions. The ability of proteins and RNAs to form condensates is encoded in their sequences, yet it is unknown which domains drive the phase separation (PS) process and what are their specific roles. Here, we systematically investigated the human and yeast proteomes to find regions promoting condensation. Using advanced computational methods to predict the PS propensity of proteins, we designed a set of experiments to investigate the contributions of Prion-Like Domains (PrLDs) and RNA-binding domains (RBDs). We found that one PrLD is sufficient to drive PS, whereas multiple RBDs are needed to modulate the dynamics of the assemblies. In the case of stress granule protein Pub1 we show that the PrLD promotes sequestration of protein partners and the RBD confers liquid-like behaviour to the condensate. Our work sheds light on the fine interplay between RBDs and PrLD to regulate formation of membrane-less organelles, opening up the avenue for their manipulation.application/pdfeng© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.cominfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1093/nar/gkaa681info:eu-repo/semantics/openAccess