{"doi":"10.1016/j.molcel.2020.11.041","title":"Genomic RNA Elements Drive Phase Separation of the SARS-CoV-2 Nucleocapsid","abstract":"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.","journal":"Molecular Cell","year":2020,"id":594,"datarank":0.8845730801455112,"base_score":5.8971538676367405,"endowment":5.8971538676367405,"self_citation_contribution":0.8845730801455112,"citation_network_contribution":0.0,"self_endowment_contribution":0.8845730801455112,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":363,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0325,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-12-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":5942,"name":"Christine A. Roden","orcid":null,"position":1,"is_corresponding":false},{"id":5943,"name":"Mark A. Boerneke","orcid":"0000-0003-0092-3203","position":2,"is_corresponding":false},{"id":5945,"name":"Grace A. McLaughlin","orcid":null,"position":4,"is_corresponding":false},{"id":292,"name":"Irwin Jungreis","orcid":"0000-0002-3197-5367","position":5,"is_corresponding":false},{"id":5946,"name":"Ethan J. Fritch","orcid":"0000-0003-1096-8958","position":6,"is_corresponding":false},{"id":5947,"name":"Yixuan J. Hou","orcid":"0000-0002-8323-7243","position":7,"is_corresponding":false},{"id":5948,"name":"Joanne Ekena","orcid":"0000-0002-7759-763X","position":8,"is_corresponding":false},{"id":5949,"name":"Chase A. Weidmann","orcid":"0000-0002-2941-0500","position":9,"is_corresponding":false},{"id":5950,"name":"Chandra L. Theesfeld","orcid":"0000-0002-8379-6600","position":10,"is_corresponding":false},{"id":14693,"name":"Sharon L. R. Kardia","orcid":"0000-0002-9853-3379","position":11,"is_corresponding":false},{"id":5951,"name":"Olga G. Troyanskaya","orcid":"0000-0002-5676-5737","position":12,"is_corresponding":false},{"id":5952,"name":"Ralph S. Baric","orcid":"0000-0001-6827-8701","position":13,"is_corresponding":false},{"id":5953,"name":"Timothy P. Sheahan","orcid":"0000-0001-9181-2183","position":14,"is_corresponding":false},{"id":5954,"name":"Kevin M. Weeks","orcid":"0000-0002-6748-9985","position":15,"is_corresponding":false},{"id":5955,"name":"Amy S. Gladfelter","orcid":"0000-0002-2490-6945","position":16,"is_corresponding":false},{"id":5956,"name":"Christine Roden","orcid":"0000-0002-3750-4865","position":17,"is_corresponding":false},{"id":5957,"name":"Rachel Sealfon","orcid":"0000-0002-3007-4698","position":18,"is_corresponding":false},{"id":5941,"name":"Christiane Iserman","orcid":"0000-0001-5976-1857","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}