SARS-CoV-2 nucleocapsid protein forms condensates with viral genomic RNA.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection causes Coronavirus Disease 2019 (COVID-19), a pandemic that seriously threatens global health. SARS-CoV-2 propagates by packaging its RNA genome into membrane enclosures in host cells. The packaging of the viral genome into t...

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Autores principales:	Amanda Jack, Luke S Ferro, Michael J Trnka, Eddie Wehri, Amrut Nadgir, Xammy Nguyenla, Douglas Fox, Katelyn Costa, Sarah Stanley, Julia Schaletzky, Ahmet Yildiz
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/e271d9b371854803a475213bf879bd42
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spelling	oai:doaj.org-article:e271d9b371854803a475213bf879bd422021-12-02T19:54:20ZSARS-CoV-2 nucleocapsid protein forms condensates with viral genomic RNA.1544-91731545-788510.1371/journal.pbio.3001425https://doaj.org/article/e271d9b371854803a475213bf879bd422021-10-01T00:00:00Zhttps://doi.org/10.1371/journal.pbio.3001425https://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection causes Coronavirus Disease 2019 (COVID-19), a pandemic that seriously threatens global health. SARS-CoV-2 propagates by packaging its RNA genome into membrane enclosures in host cells. The packaging of the viral genome into the nascent virion is mediated by the nucleocapsid (N) protein, but the underlying mechanism remains unclear. Here, we show that the N protein forms biomolecular condensates with viral genomic RNA both in vitro and in mammalian cells. While the N protein forms spherical assemblies with homopolymeric RNA substrates that do not form base pairing interactions, it forms asymmetric condensates with viral RNA strands. Cross-linking mass spectrometry (CLMS) identified a region that drives interactions between N proteins in condensates, and deletion of this region disrupts phase separation. We also identified small molecules that alter the size and shape of N protein condensates and inhibit the proliferation of SARS-CoV-2 in infected cells. These results suggest that the N protein may utilize biomolecular condensation to package the SARS-CoV-2 RNA genome into a viral particle.Amanda JackLuke S FerroMichael J TrnkaEddie WehriAmrut NadgirXammy NguyenlaDouglas FoxKatelyn CostaSarah StanleyJulia SchaletzkyAhmet YildizPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 19, Iss 10, p e3001425 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Amanda Jack Luke S Ferro Michael J Trnka Eddie Wehri Amrut Nadgir Xammy Nguyenla Douglas Fox Katelyn Costa Sarah Stanley Julia Schaletzky Ahmet Yildiz SARS-CoV-2 nucleocapsid protein forms condensates with viral genomic RNA.
description	The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection causes Coronavirus Disease 2019 (COVID-19), a pandemic that seriously threatens global health. SARS-CoV-2 propagates by packaging its RNA genome into membrane enclosures in host cells. The packaging of the viral genome into the nascent virion is mediated by the nucleocapsid (N) protein, but the underlying mechanism remains unclear. Here, we show that the N protein forms biomolecular condensates with viral genomic RNA both in vitro and in mammalian cells. While the N protein forms spherical assemblies with homopolymeric RNA substrates that do not form base pairing interactions, it forms asymmetric condensates with viral RNA strands. Cross-linking mass spectrometry (CLMS) identified a region that drives interactions between N proteins in condensates, and deletion of this region disrupts phase separation. We also identified small molecules that alter the size and shape of N protein condensates and inhibit the proliferation of SARS-CoV-2 in infected cells. These results suggest that the N protein may utilize biomolecular condensation to package the SARS-CoV-2 RNA genome into a viral particle.
format	article
author	Amanda Jack Luke S Ferro Michael J Trnka Eddie Wehri Amrut Nadgir Xammy Nguyenla Douglas Fox Katelyn Costa Sarah Stanley Julia Schaletzky Ahmet Yildiz
author_facet	Amanda Jack Luke S Ferro Michael J Trnka Eddie Wehri Amrut Nadgir Xammy Nguyenla Douglas Fox Katelyn Costa Sarah Stanley Julia Schaletzky Ahmet Yildiz
author_sort	Amanda Jack
title	SARS-CoV-2 nucleocapsid protein forms condensates with viral genomic RNA.
title_short	SARS-CoV-2 nucleocapsid protein forms condensates with viral genomic RNA.
title_full	SARS-CoV-2 nucleocapsid protein forms condensates with viral genomic RNA.
title_fullStr	SARS-CoV-2 nucleocapsid protein forms condensates with viral genomic RNA.
title_full_unstemmed	SARS-CoV-2 nucleocapsid protein forms condensates with viral genomic RNA.
title_sort	sars-cov-2 nucleocapsid protein forms condensates with viral genomic rna.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/e271d9b371854803a475213bf879bd42
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SARS-CoV-2 nucleocapsid protein forms condensates with viral genomic RNA.

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