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  Nucleocapsid protein of SARS-CoV-2 phase separates into RNA-rich polymerase-containing condensates

Savastano, A., Ibanez de Opakua, A., Rankovic, M., & Zweckstetter, M. (2020). Nucleocapsid protein of SARS-CoV-2 phase separates into RNA-rich polymerase-containing condensates. Nature Communications, 11: 6041. doi:10.1038/s41467-020-19843-1.

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Savastano, A.1, Author           
Ibanez de Opakua, A.1, Author           
Rankovic, M.1, Author           
Zweckstetter, M.2, Author           
Affiliations:
1Research Group of Protein Structure Determination using NMR, MPI for Biophysical Chemistry, Max Planck Society, ou_578571              
2Research Group of Protein Structure Determination using NMR, MPI for biophysical chemistry, Max Planck Society, ou_578571              

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Free keywords: Intrinsically disordered proteins; Solution-state NMR; Structural biology
 Abstract: The etiologic agent of the Covid-19 pandemic is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The viral membrane of SARS-CoV-2 surrounds a helical nucleocapsid in which the viral genome is encapsulated by the nucleocapsid protein. The nucleocapsid protein of SARS-CoV-2 is produced at high levels within infected cells, enhances the efficiency of viral RNA transcription, and is essential for viral replication. Here, we show that RNA induces cooperative liquid–liquid phase separation of the SARS-CoV-2 nucleocapsid protein. In agreement with its ability to phase separate in vitro, we show that the protein associates in cells with stress granules, cytoplasmic RNA/protein granules that form through liquid-liquid phase separation and are modulated by viruses to maximize replication efficiency. Liquid–liquid phase separation generates high-density protein/RNA condensates that recruit the RNA-dependent RNA polymerase complex of SARS-CoV-2 providing a mechanism for efficient transcription of viral RNA. Inhibition of RNA-induced phase separation of the nucleocapsid protein by small molecules or biologics thus can interfere with a key step in the SARS-CoV-2 replication cycle.

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Language(s): eng - English
 Dates: 2020-11-27
 Publication Status: Published online
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 Rev. Type: Peer
 Identifiers: DOI: 10.1038/s41467-020-19843-1
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Title: Nature Communications
Source Genre: Journal
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Pages: 10 Volume / Issue: 11 Sequence Number: 6041 Start / End Page: - Identifier: -