| Autor: |
Boerneke, M.A., Weidmann, C.A., Sheahan, T.P., Hou, Y.J., Ekena, J., Baric, R.S., Troyanskaya, O.G., Jungreis, I., Gladfelter, A.S., Sealfon, R.S.G., Kellis, M., Roden, C.A., Weeks, K.M., Iserman, C., Theesfeld, C.L., Fritch, E.J., McLaughlin, G.A. |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| DOI: |
10.17615/cxx3-s559 |
| Popis: |
We report that the SARS-CoV-2 nucleocapsid protein (N-protein) undergoes liquid-liquid phase separation (LLPS) with viral RNA. N-protein condenses with specific RNA genomic elements under physiological buffer conditions and condensation is enhanced at human body temperatures (33��C and 37��C) and reduced at room temperature (22��C). RNA sequence and structure in specific genomic regions regulate N-protein condensation while other genomic regions promote condensate dissolution, potentially preventing aggregation of the large genome. At low concentrations, N-protein preferentially crosslinks to specific regions characterized by single-stranded RNA flanked by structured elements and these features specify the location, number, and strength of N-protein binding sites (valency). 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 RNA sequence and structure specific, sensitive to human body temperature, and manipulatable with small molecules, and therefore presents a screenable process for identifying antiviral compounds effective against SARS-CoV-2. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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