{"doi":"10.17615/rg26-vy94","title":"Differential hepatitis C virus RNA target site selection and host factor activities of naturally occurring miR-122 3′ variants","abstract":"In addition to suppressing cellular gene expression, certain miRNAs potently facilitate replication of specific positive-strand RNA viruses. miR-122, a pro-viral hepatitis C virus (HCV) host factor, binds and recruits Ago2 to tandem sites (S1 and S2) near the 5΄ end of the HCV genome, stabilizing it and promoting its synthesis. HCV target site selection follows canonical miRNA rules, but how non-templated 3΄ miR-122 modifications impact this unconventional miRNA action is unknown. High-throughput sequencing revealed that a 22 nt miRNA with 3΄G (‘22–3΄G’) comprised <63% of total miR-122 in human liver, whereas other variants (23–3΄A, 23–3΄U, 21–3΄U) represented 11–17%. All loaded equivalently into Ago2, and when tested individually functioned comparably in suppressing gene expression. In contrast, 23–3΄A and 23–3΄U were more active than 22–3΄G in stabilizing HCV RNA and promoting its replication, whereas 21–3΄U was almost completely inactive. This lack of 21–3΄U HCV host factor activity correlated with reduced recruitment of Ago2 to the HCV S1 site. Additional experiments demonstrated strong preference for guanosine at nt 22 of miR-122. Our findings reveal the importance of non-templated 3΄ miR-122 modifications to its HCV host factor activity, and identify unexpected differences in miRNA requirements for host gene suppression versus RNA virus replication.","journal":"UNC Libraries","year":2020,"id":116168,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9496,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":543879,"name":"Mi Zhou","orcid":"0000-0002-7462-5463","position":1,"is_corresponding":false},{"id":58371,"name":"Praveen Sethupathy","orcid":"0000-0002-7983-239X","position":2,"is_corresponding":false},{"id":520808,"name":"You Li","orcid":"0000-0001-5458-6009","position":3,"is_corresponding":false},{"id":543880,"name":"Daisuke Yamane","orcid":"0000-0003-1592-9368","position":4,"is_corresponding":false},{"id":445381,"name":"Sara R. Selitsky","orcid":"0000-0001-8765-5269","position":5,"is_corresponding":false},{"id":415265,"name":"Stanley M. Lemon","orcid":"0000-0003-1450-806X","position":6,"is_corresponding":false},{"id":543881,"name":"Tetsuro Shimakami","orcid":"0000-0002-8308-4056","position":7,"is_corresponding":false},{"id":543878,"name":"Masao Honda","orcid":"0000-0003-3050-5854","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:13:44.286758Z","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":[]}