Title | Competing Protein-RNA Interaction Networks Control Multiphase Intracellular Organization. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Sanders, DW, Kedersha, N, Lee, DSW, Strom, AR, Drake, V, Riback, JA, Bracha, D, Eeftens, JM, Iwanicki, A, Wang, A, Wei, M-T, Whitney, G, Lyons, SM, Anderson, P, Jacobs, WM, Ivanov, P, Brangwynne, CP |
Journal | Cell |
Volume | 181 |
Issue | 2 |
Pagination | 306-324.e28 |
Date Published | 2020 04 16 |
ISSN | 1097-4172 |
Keywords | Biophysical Phenomena, Cell Line, Tumor, Cytoplasm, Cytoplasmic Granules, Cytoplasmic Structures, Humans, Intrinsically Disordered Proteins, Liquid-Liquid Extraction, Organelles, Protein Interaction Maps, RNA, RNA Recognition Motif Proteins |
Abstract | <p>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.</p> |
DOI | 10.1016/j.cell.2020.03.050 |
Alternate Journal | Cell |
PubMed ID | 32302570 |
Grant List | R00 GM124458 / GM / NIGMS NIH HHS / United States / HHMI / Howard Hughes Medical Institute / United States R35 GM126901 / GM / NIGMS NIH HHS / United States U01 DA040601 / DA / NIDA NIH HHS / United States F32 GM130072 / GM / NIGMS NIH HHS / United States K99 GM124458 / GM / NIGMS NIH HHS / United States R01 GM126150 / GM / NIGMS NIH HHS / United States |