Specific viral RNA drives the SARS CoV-2 nucleocapsid to phase separate.

Autor:	Iserman C; Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Roden C; Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Boerneke M; Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Sealfon R; Flatiron Institute, Simons Foundation, New York, NY, USA., McLaughlin G; Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Jungreis I; Broad Institute, MIT, Cambridge, MA, USA., Park C; Flatiron Institute, Simons Foundation, New York, NY, USA., Boppana A; Department of Computer Science, Princeton University, Princeton, NJ USA., Fritch E; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Hou YJ; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Theesfeld C; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ USA., Troyanskaya OG; Flatiron Institute, Simons Foundation, New York, NY, USA.; Department of Computer Science, Princeton University, Princeton, NJ USA.; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ USA., Baric RS; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Sheahan TP; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Weeks K; Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Gladfelter AS; Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2020 Jun 12. Date of Electronic Publication: 2020 Jun 12.
DOI:	10.1101/2020.06.11.147199
Abstrakt:	A mechanistic understanding of the SARS-CoV-2 viral replication cycle is essential to develop new therapies for the COVID-19 global health crisis. In this study, we show that the SARS-CoV-2 nucleocapsid protein (N-protein) undergoes liquid-liquid phase separation (LLPS) with the viral genome, and propose a model of viral packaging through LLPS. N-protein condenses with specific RNA sequences in the first 1000 nts (5'-End) under physiological conditions and is enhanced at human upper airway temperatures. N-protein condensates exclude non-packaged RNA sequences. We comprehensively map sites bound by N-protein in the 5'-End and find preferences for single-stranded RNA flanked by stable structured elements. Liquid-like N-protein condensates form in mammalian cells in a concentration-dependent manner and can be altered by small molecules. Condensation of N-protein is sequence and structure specific, sensitive to human body temperature, and manipulatable with small molecules thus presenting screenable processes for identifying antiviral compounds effective against SARS-CoV-2. Competing Interests: Competing interests: K.M.W. is an advisor to and holds equity in Ribometrix, to which mutational profiling (MaP) technologies have been licensed. All other authors declare that they have no competing interests.
Databáze:	MEDLINE
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