įunding: This project has received funding from the European Research Council (ERC) under the European Union Horizon 2020 research and innovation programme (grant agreement No 803326 to R.C.G). All the codes for our models are already shared in GitHub. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: All relevant data are within the manuscript and its Supporting information files. Received: OctoAccepted: JanuPublished: February 2, 2022Ĭopyright: © 2022 Sanchez-Burgos et al. Overall, our work sheds light on the molecular and physicochemical mechanisms by which condensate stability is impacted by RNA of different lengths.Ĭitation: Sanchez-Burgos I, Espinosa JR, Joseph JA, Collepardo-Guevara R (2022) RNA length has a non-trivial effect in the stability of biomolecular condensates formed by RNA-binding proteins. Our simulations reveal that phase separation of RNA-binding proteins is RNA-length dependent only when heterotypic protein–RNA interactions have a comparable or higher contribution towards the connectivity of the condensate liquid network than the homotypic protein–protein interactions. To do so, we develop a multiscale computational strategy that integrates a sequence-dependent protein/RNA coarse-grained model and minimal representation of proteins as patchy particles. Here, we focus on single-stranded disordered RNAs and uncover the role that RNA strand length has in promoting phase separation of RNA-binding proteins. In vivo, RNAs vary enourmously in sequence, structure, and length. RNA strands can promote or inhibit phase separation of RNA-binding proteins in a concentration-dependent manner. Nucleic acids, which are ubiquitously found in condensates, can act as critical modulators in the stability of protein condensates. Liquid–liquid phase separation of proteins and other biomolecules into condensed phases has emerged as a fundamental mechanism to organize biological matter in living cells. Taken together, our results contribute to illuminate the intricate physicochemical mechanisms that influence the stability of RBP condensates through RNA inclusion. Phase separation is RNA-length dependent whenever the relative contribution of heterotypic interactions sustaining LLPS is comparable or higher than those stemming from protein homotypic interactions. Our minimal patchy particle simulations suggest that the strikingly different effect of RNA length on homotypic LLPS versus RBP–RNA complex coacervation is general. In contrast, the 25-repeat proline-arginine peptide (PR 25), which does not undergo LLPS on its own at physiological conditions but instead exhibits complex coacervation with RNA-i.e., via heterotypic interactions-shows a strong dependence on the length of the RNA strands. We find that for a constant nucleotide/protein ratio, the protein fused in sarcoma (FUS), which can phase separate on its own-i.e., via homotypic interactions-only exhibits a mild dependency on the RNA strand length. To unveil the role of RNA length in regulating the stability of RNA binding protein (RBP) condensates, we present a multiscale computational strategy that exploits the advantages of a sequence-dependent coarse-grained representation of proteins and a minimal coarse-grained model wherein proteins are described as patchy colloids. Nucleic acids can act as critical modulators in the stability of these protein condensates. Biomolecular condensates formed via liquid–liquid phase separation (LLPS) play a crucial role in the spatiotemporal organization of the cell material.
0 kommentar(er)
