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bioRxiv · 10.1101/2020.06.28.176248

Phosphorylation modulates liquid-liquid phase separation of the SARS-CoV-2 N protein

Carlson, C. R.·Asfaha, J. B.·Ghent, C. M.·Howard, C. J.·Hartooni, N.·Morgan, D. O.
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Abstract

The nucleocapsid (N) protein of coronaviruses serves two major functions: compaction of the RNA genome in the virion and regulation of viral gene transcription in the infected cell1–3. The N protein contains two globular RNA-binding domains surrounded by regions of intrinsic disorder4. Phosphorylation of the central disordered region is required for normal viral genome transcription5,6, which occurs in a cytoplasmic structure called the replication transcription complex (RTC)7–11. It is not known how phosphorylation controls N protein function. Here we show that the N protein of SARS-CoV-2, together with viral RNA, forms biomolecular condensates12–15. Unmodified N protein forms partially ordered gel-like structures that depend on multivalent RNA-protein and protein-protein interactions. Phosphorylation reduces a subset of these interactions, generating a more liquid-like droplet. We speculate that distinct oligomeric states support the two functions of the N protein: unmodified protein forms a structured oligomer that is suited for nucleocapsid assembly, and phosphorylated protein forms a liquid-like compartment for viral genome processing. Inhibitors of N protein phosphorylation could therefore serve as antiviral therapy.Competing Interest StatementThe authors have declared no competing interest.View Full Text

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Carlson, C. R., Asfaha, J. B., Ghent, C. M., Howard, C. J., Hartooni, N., Morgan, D. O.. 2020-06-29. Phosphorylation modulates liquid-liquid phase separation of the SARS-CoV-2 N protein. https://doi.org/10.1101/2020.06.28.176248

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