RNA-binding and prion domains: the Yin and Yang of phase separation

Lorenzo Gotor, Maria de las Nieves; Armaos, Alexandros, 1989-; Calloni, Giulia; Torrent Burgas, Marc; Vabulas, R. Martin; Sánchez de Groot, Natalia; Tartaglia, Gian Gaetano

doi:http://dx.doi.org/10.1093/nar/gkaa681

RNA-binding and prion domains: the Yin and Yang of phase separation

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Lorenzo 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/gkaa681

Abstract

Proteins 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.