Competing Protein-RNA Interaction Networks Control Multiphase Intracellular Organization.

Autor:	Sanders DW; Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA., Kedersha N; Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA., Lee DSW; Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA., Strom AR; Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA., Drake V; Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA., Riback JA; Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA., Bracha D; Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA., Eeftens JM; Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA., Iwanicki A; Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA., Wang A; Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA., Wei MT; Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA., Whitney G; Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA., Lyons SM; Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA., Anderson P; Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA., Jacobs WM; Department of Chemistry, Princeton University, Princeton, NJ 08544, USA., Ivanov P; Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA., Brangwynne CP; Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA; Howard Hughes Medical Institute, Princeton, NJ 08544, USA. Electronic address: cbrangwy@princeton.edu.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2020 Apr 16; Vol. 181 (2), pp. 306-324.e28.
DOI:	10.1016/j.cell.2020.03.050
Abstrakt:	Liquid-liquid phase separation (LLPS) mediates formation of membraneless condensates such as those associated with RNA processing, but the rules that dictate their assembly, substructure, and coexistence with other liquid-like compartments remain elusive. Here, we address the biophysical mechanism of this multiphase organization using quantitative reconstitution of cytoplasmic stress granules (SGs) with attached P-bodies in human cells. Protein-interaction networks can be viewed as interconnected complexes (nodes) of RNA-binding domains (RBDs), whose integrated RNA-binding capacity determines whether LLPS occurs upon RNA influx. Surprisingly, both RBD-RNA specificity and disordered segments of key proteins are non-essential, but modulate multiphase condensation. Instead, stoichiometry-dependent competition between protein networks for connecting nodes determines SG and P-body composition and miscibility, while competitive binding of unconnected proteins disengages networks and prevents LLPS. Inspired by patchy colloid theory, we propose a general framework by which competing networks give rise to compositionally specific and tunable condensates, while relative linkage between nodes underlies multiphase organization. Competing Interests: Declaration of Interests Patent applications have been filed based on this work. (Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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