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      Active coacervate droplets as a model for membraneless organelles and protocells

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          Abstract

          Membraneless organelles like stress granules are active liquid-liquid phase-separated droplets that are involved in many intracellular processes. Their active and dynamic behavior is often regulated by ATP-dependent reactions. However, how exactly membraneless organelles control their dynamic composition remains poorly understood. Herein, we present a model for membraneless organelles based on RNA-containing active coacervate droplets regulated by a fuel-driven reaction cycle. These droplets emerge when fuel is present, but decay without. Moreover, we find these droplets can transiently up-concentrate functional RNA which remains in its active folded state inside the droplets. Finally, we show that in their pathway towards decay, these droplets break apart in multiple droplet fragments. Emergence, decay, rapid exchange of building blocks, and functionality are all hallmarks of membrane-less organelles, and we believe that our work could be powerful as a model to study such organelles.

          Abstract

          Membraneless organelles are liquid-liquid phase-separated droplets whose behaviour can be regulated by chemical reactions, but this process is poorly understood. Here, the authors report model membraneless organelles based on coacervate droplets that show fuel-driven dynamic behaviour and concentrate functional RNA.

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          Most cited references59

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          Biomolecular condensates: organizers of cellular biochemistry

          In addition to membrane-bound organelles, eukaryotic cells feature various membraneless compartments, including the centrosome, the nucleolus and various granules. Many of these compartments form through liquid–liquid phase separation, and the principles, mechanisms and regulation of their assembly as well as their cellular functions are now beginning to emerge.
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            Liquid phase condensation in cell physiology and disease.

            Phase transitions are ubiquitous in nonliving matter, and recent discoveries have shown that they also play a key role within living cells. Intracellular liquid-liquid phase separation is thought to drive the formation of condensed liquid-like droplets of protein, RNA, and other biomolecules, which form in the absence of a delimiting membrane. Recent studies have elucidated many aspects of the molecular interactions underlying the formation of these remarkable and ubiquitous droplets and the way in which such interactions dictate their material properties, composition, and phase behavior. Here, we review these exciting developments and highlight key remaining challenges, particularly the ability of liquid condensates to both facilitate and respond to biological function and how their metastability may underlie devastating protein aggregation diseases.
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              Germline P granules are liquid droplets that localize by controlled dissolution/condensation.

              In sexually reproducing organisms, embryos specify germ cells, which ultimately generate sperm and eggs. In Caenorhabditis elegans, the first germ cell is established when RNA and protein-rich P granules localize to the posterior of the one-cell embryo. Localization of P granules and their physical nature remain poorly understood. Here we show that P granules exhibit liquid-like behaviors, including fusion, dripping, and wetting, which we used to estimate their viscosity and surface tension. As with other liquids, P granules rapidly dissolved and condensed. Localization occurred by a biased increase in P granule condensation at the posterior. This process reflects a classic phase transition, in which polarity proteins vary the condensation point across the cell. Such phase transitions may represent a fundamental physicochemical mechanism for structuring the cytoplasm.
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                Author and article information

                Contributors
                job.boekhoven@tum.de
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                14 October 2020
                14 October 2020
                2020
                : 11
                : 5167
                Affiliations
                [1 ]GRID grid.6936.a, ISNI 0000000123222966, Department of Chemistry, , Technical University of Munich, Lichtenbergstrasse 4, ; 85748 Garching, Germany
                [2 ]GRID grid.6936.a, ISNI 0000000123222966, Institute for Advanced Study, , Technical University of Munich, Lichtenbergstrasse 2a, ; 85748 Garching, Germany
                [3 ]GRID grid.4567.0, ISNI 0000 0004 0483 2525, Institute of Structural Biology, , Helmholtz Zentrum München, Ingolstädter Landstrasse 1, ; 85764 Neuherberg, Germany
                [4 ]GRID grid.418615.f, ISNI 0000 0004 0491 845X, Max Planck Institute of Biochemistry, Am Klopferspitz 18, ; 82152 Martinsried, Germany
                Author information
                http://orcid.org/0000-0003-4029-5096
                http://orcid.org/0000-0001-8005-1657
                http://orcid.org/0000-0002-9126-2430
                Article
                18815
                10.1038/s41467-020-18815-9
                7560875
                33056997
                c8199405-ef98-4c8a-80ac-21e79051cbd0
                © The Author(s) 2020

                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/.

                History
                : 21 February 2020
                : 9 September 2020
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100001659, Deutsche Forschungsgemeinschaft (German Research Foundation);
                Award ID: Project-16 364653263 – TRR 235
                Award Recipient :
                Categories
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                © The Author(s) 2020

                Uncategorized
                origin of life,self-assembly
                Uncategorized
                origin of life, self-assembly

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