SARS-CoV-2 nucleocapsid protein phase-separates with RNA and with human hnRNPs.

Autor: Perdikari TM; Center for Biomedical Engineering, Brown University, Providence, RI, USA., Murthy AC; Molecular Biology, Cell Biology & Biochemistry Graduate Program, Brown University, Providence, RI, USA., Ryan VH; Neuroscience Graduate Program, Brown University, Providence, RI, USA., Watters S; Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, RI, USA., Naik MT; Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, RI, USA., Fawzi NL; Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, RI, USA.; Robert J. and Nancy D. Carney Institute for Brain Science, Brown University, Providence, RI, USA.
Jazyk: angličtina
Zdroj: The EMBO journal [EMBO J] 2020 Dec 15; Vol. 39 (24), pp. e106478. Date of Electronic Publication: 2020 Dec 04.
DOI: 10.15252/embj.2020106478
Abstrakt: Tightly packed complexes of nucleocapsid protein and genomic RNA form the core of viruses and assemble within viral factories, dynamic compartments formed within the host cells associated with human stress granules. Here, we test the possibility that the multivalent RNA-binding nucleocapsid protein (N) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) condenses with RNA via liquid-liquid phase separation (LLPS) and that N protein can be recruited in phase-separated forms of human RNA-binding proteins associated with SG formation. Robust LLPS with RNA requires two intrinsically disordered regions (IDRs), the N-terminal IDR and central-linker IDR, as well as the folded C-terminal oligomerization domain, while the folded N-terminal domain and the C-terminal IDR are not required. N protein phase separation is induced by addition of non-specific RNA. In addition, N partitions in vitro into phase-separated forms of full-length human hnRNPs (TDP-43, FUS, hnRNPA2) and their low-complexity domains (LCs). These results provide a potential mechanism for the role of N in SARS-CoV-2 viral genome packing and in host-protein co-opting necessary for viral replication and infectivity.
(© 2020 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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