@article{4022,
  keywords = {Animals, RNA, Viral, Humans, Phosphoproteins, HEK293 Cells, Vero Cells, Genome, Viral, Chlorocebus aethiops, Antiviral Agents, Drug Evaluation, Preclinical, COVID-19, SARS-CoV-2, Coronavirus Nucleocapsid Proteins, Nucleocapsid, COVID-19 Drug Treatment},
  author = {Christiane Iserman and Christine Roden and Mark Boerneke and Rachel Sealfon and Grace McLaughlin and Irwin Jungreis and Ethan Fritch and Yixuan Hou and Joanne Ekena and Chase Weidmann and Chandra Theesfeld and Manolis Kellis and Olga Troyanskaya and Ralph Baric and Timothy Sheahan and Kevin Weeks and Amy Gladfelter},
  title = {Genomic RNA Elements Drive Phase Separation of the SARS-CoV-2 Nucleocapsid.},
  abstract = { <p>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{\textdegree}C and 37{\textdegree}C) and reduced at room temperature (22{\textdegree}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.</p> },
  year = {2020},
  journal = {Mol Cell},
  volume = {80},
  pages = {1078-1091.e6},
  month = {2020 Dec 17},
  issn = {1097-4164},
  doi = {10.1016/j.molcel.2020.11.041},
  language = {eng},
}