tetano
Editor, Senior Moderator
PLoS Biol
. 2021 Oct 11;19(10):e3001425.
doi: 10.1371/journal.pbio.3001425. Online ahead of print.
SARS-CoV-2 nucleocapsid protein forms condensates with viral genomic RNA
Amanda Jack[SUP] 1 [/SUP], Luke S Ferro[SUP] 2 [/SUP], Michael J Trnka[SUP] 3 [/SUP], Eddie Wehri[SUP] 4 [/SUP], Amrut Nadgir[SUP] 5 [/SUP], Xammy Nguyenla[SUP] 6 [/SUP], Douglas Fox[SUP] 6 [/SUP], Katelyn Costa[SUP] 7 [/SUP], Sarah Stanley[SUP] 2 6 [/SUP], Julia Schaletzky[SUP] 4 [/SUP], Ahmet Yildiz[SUP] 1 2 5 [/SUP]
Affiliations
Abstract
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 forms interactions between N proteins in condensates, and truncation of this region disrupts phase separation. We also identified small molecules that alter the formation 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.
. 2021 Oct 11;19(10):e3001425.
doi: 10.1371/journal.pbio.3001425. Online ahead of print.
SARS-CoV-2 nucleocapsid protein forms condensates with viral genomic RNA
Amanda Jack[SUP] 1 [/SUP], Luke S Ferro[SUP] 2 [/SUP], Michael J Trnka[SUP] 3 [/SUP], Eddie Wehri[SUP] 4 [/SUP], Amrut Nadgir[SUP] 5 [/SUP], Xammy Nguyenla[SUP] 6 [/SUP], Douglas Fox[SUP] 6 [/SUP], Katelyn Costa[SUP] 7 [/SUP], Sarah Stanley[SUP] 2 6 [/SUP], Julia Schaletzky[SUP] 4 [/SUP], Ahmet Yildiz[SUP] 1 2 5 [/SUP]
Affiliations
- PMID: 34634033
- DOI: 10.1371/journal.pbio.3001425
Abstract
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 forms interactions between N proteins in condensates, and truncation of this region disrupts phase separation. We also identified small molecules that alter the formation 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.