{"doi":"10.1101/2022.09.27.509633","title":"Nuclear translocation of spike mRNA and protein is a novel pathogenic feature of SARS-CoV-2","abstract":"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes severe pathophysiology in vulnerable older populations and appears to be highly pathogenic and more transmissible than SARS-CoV or MERS-CoV [1, 2]. The spike (S) protein appears to be a major pathogenic factor that contributes to the unique pathogenesis of SARS-CoV-2. Although the S protein is a surface transmembrane type 1 glycoprotein, it has been predicted to be translocated into the nucleus due to the novel nuclear localization signal (NLS) \"PRRARSV\", which is absent from the S protein of other coronaviruses. Indeed, S proteins translocate into the nucleus in SARS-CoV-2-infected cells. To our surprise, S mRNAs also translocate into the nucleus. S mRNA colocalizes with S protein, aiding the nuclear translocation of S mRNA. While nuclear translocation of nucleoprotein (N) has been shown in many coronaviruses, the nuclear translocation of both S mRNA and S protein reveals a novel pathogenic feature of SARS-CoV-2. Author summary: One of the novel sequence insertions resides at the S1/S2 boundary of Spike (S) protein and constitutes a functional nuclear localization signal (NLS) motif \"PRRARSV\", which may supersede the importance of previously proposed polybasic furin cleavage site \"RRAR\". Indeed, S protein's NLS-driven nuclear translocation and its possible role in S mRNA's nuclear translocation reveal a novel pathogenic feature of SARS-CoV-2.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":298852,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.958,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":243363,"name":"Juraj Kabát","orcid":"0000-0001-8636-542X","position":1,"is_corresponding":false},{"id":554346,"name":"Kailey Jerome","orcid":"0000-0003-3649-1596","position":2,"is_corresponding":false},{"id":107169,"name":"Friederike Feldmann","orcid":"0000-0002-1363-1077","position":3,"is_corresponding":false},{"id":326353,"name":"Kristina L. Bailey","orcid":"0000-0003-2990-9042","position":4,"is_corresponding":false},{"id":554347,"name":"Masfique Mehedi","orcid":"0000-0003-1728-3126","position":5,"is_corresponding":false},{"id":988790,"name":"Sarah Sattar","orcid":null,"position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-19T00:31:40.528568Z","pmid":"36203551","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":[]}