{"doi":"10.1128/jvi.00738-14","title":"Dependence of Coronavirus RNA Replication on an NH\n            <sub>2</sub>\n            -Terminal Partial Nonstructural Protein 1 in\n            <i>cis</i>","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            Genomes of positive (+)-strand RNA viruses use\n            <jats:italic>cis</jats:italic>\n            -acting signals to direct both translation and replication. Here we examine two 5′-proximal\n            <jats:italic>cis</jats:italic>\n            -replication signals of different character in a defective interfering (DI) RNA of the bovine coronavirus (BCoV) that map within a 322-nucleotide (nt) sequence (136 nt from the genomic 5′ untranslated region and 186 nt from the nonstructural protein 1 [nsp1]-coding region) not found in the otherwise-identical nonreplicating subgenomic mRNA7 (sgmRNA7). The natural DI RNA is structurally a fusion of the two ends of the BCoV genome that results in a single open reading frame between a partial nsp1-coding region and the entire N gene. (i) In the first examination, mutation analyses of a recently discovered long-range RNA-RNA base-paired structure between the 5′ untranslated region and the partial nsp1-coding region showed that it, possibly in concert with adjacent stem-loops, is a\n            <jats:italic>cis</jats:italic>\n            -acting replication signal in the (+) strand. We postulate that the higher-order structure promotes (+)-strand synthesis. (ii) In the second examination, analyses of multiple frame shifts, truncations, and point mutations within the partial nsp1-coding region showed that synthesis of a PEFP core amino acid sequence within a group A lineage betacoronavirus-conserved NH\n            <jats:sub>2</jats:sub>\n            -proximal WAPEFPWM domain is required in\n            <jats:italic>cis</jats:italic>\n            for DI RNA replication. We postulate that the nascent protein, as part of an RNA-associated translating complex, acts to direct the DI RNA to a critical site, enabling RNA replication. We suggest that these results have implications for viral genome replication and explain, in part, why coronavirus sgmRNAs fail to replicate.\n          </jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE</jats:bold>\n            <jats:italic>cis</jats:italic>\n            -Acting RNA and protein structures that regulate (+)-strand RNA virus genome synthesis are potential sites for blocking virus replication. Here we describe two: a previously suspected 5′-proximal long-range higher-order RNA structure and a novel nascent NH\n            <jats:sub>2</jats:sub>\n            -terminal protein component of nsp1 that are common among betacoronaviruses of group A lineage.\n          </jats:p>","journal":"Journal of Virology","year":2014,"id":35637,"datarank":0.4722598690876003,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.1803733467293033,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.1803733467293033,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":6,"citers_with_citation_signal":6,"citers_with_endowment":6,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":182108,"name":"Yi-Hsin Fan","orcid":null,"position":1,"is_corresponding":false},{"id":182109,"name":"David A. Brian","orcid":null,"position":2,"is_corresponding":false},{"id":182107,"name":"Yu-Pin Su","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"24872586","pmcid":"PMC4136265","openalex_id":"https://openalex.org/W2124358327","authors":[],"funders":[{"funder_name":"NIAID NIH HHS","grant_id":"AI 14376","title":null}],"total_grants":1,"fwci":2.1559,"citation_percentile":0.86549895,"influential_citations":2,"citation_trend":[{"year":2014,"count":2},{"year":2015,"count":2},{"year":2016,"count":1},{"year":2024,"count":1}],"oa_status":"green","license":"https://journals.asm.org/non-commercial-tdm-license","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4136265","host_type":"repository"},{"url":"https://europepmc.org/articles/pmc4136265?pdf=render","host_type":"GREEN"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4136265","host_type":"repository"},{"url":"https://journals.asm.org/doi/pdf/10.1128/JVI.00738-14","host_type":"publisher"},{"url":"https://doi.org/10.1128/jvi.00738-14","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/24872586","host_type":"repository"},{"url":"http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.1008.2251","host_type":""}],"fields_of_study":["Animal Virus Infections Studies","SARS-CoV-2 and COVID-19 Research","Viral gastroenteritis research and epidemiology","Biology","Medicine","5' Untranslated Regions","Amino Acid Sequence","Base Pairing","Base Sequence","Cell Line, Tumor","Coronavirus Infections","Coronavirus, Bovine","Genome, Viral","Humans","Molecular Sequence Data","Open Reading Frames","RNA, Viral","Viral Nonstructural Proteins","Virus Replication"],"mesh_terms":["Amino Acid Sequence","Base Sequence","Humans","Molecular Sequence Data","RNA, Viral","Virus Replication","Open Reading Frames","Genome, Viral","Viral Nonstructural Proteins","Coronavirus, Bovine","Coronavirus Infections","Base Pairing","5' Untranslated Regions","Cell Line, Tumor"],"keywords":["Biology","Subgenomic mRNA","RNA","Genetics","Origin of replication","Non-coding RNA","Untranslated region","RNA-dependent RNA polymerase","Open reading frame","Coronavirus","Viral replication","Gene","Genome","Peptide sequence","Virus"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"gen"},{"name":"refseq"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-10T06:13:24.645608Z","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":[]}