{"doi":"10.1016/j.celrep.2022.110434","title":"The RNA helicase DHX16 recognizes specific viral RNA to trigger RIG-I-dependent innate antiviral immunity","abstract":"Type I interferons (IFN-I) are essential to establish antiviral innate immunity. Unanchored (or free) polyubiquitin (poly-Ub) has been shown to regulate IFN-I responses. However, few unanchored poly-Ub interactors are known. To identify factors regulated by unanchored poly-Ub in a physiological setting, we developed an approach to isolate unanchored poly-Ub from lung tissue. We identified the RNA helicase DHX16 as a potential pattern recognition receptor (PRR). Silencing of DHX16 in cells and in vivo diminished IFN-I responses against influenza virus. These effects extended to members of other virus families, including Zika and SARS-CoV-2. DHX16-dependent IFN-I production requires RIG-I and unanchored K48-poly-Ub synthesized by the E3-Ub ligase TRIM6. DHX16 recognizes a signal in influenza RNA segments that undergo splicing and requires its RNA helicase motif for direct, high-affinity interactions with specific viral RNAs. Our study establishes DHX16 as a PRR that partners with RIG-I for optimal activation of antiviral immunity requiring unanchored poly-Ub.","journal":"Cell Reports","year":2022,"id":246771,"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":36,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9617,"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":546873,"name":"Preeti Bharaj","orcid":"0000-0002-9411-9373","position":1,"is_corresponding":false},{"id":254583,"name":"Sarah van Tol","orcid":"0000-0002-9905-920X","position":2,"is_corresponding":false},{"id":254581,"name":"María I. Giraldo","orcid":"0000-0002-9736-3160","position":3,"is_corresponding":false},{"id":850037,"name":"María González-Orozco","orcid":"0000-0001-7299-3361","position":4,"is_corresponding":false},{"id":883513,"name":"Karl M. Valerdi","orcid":"0000-0002-7160-2602","position":5,"is_corresponding":false},{"id":883514,"name":"Abbey N. Warren","orcid":"0000-0002-5838-0208","position":6,"is_corresponding":false},{"id":233170,"name":"Leopoldo Aguilera-Aguirre","orcid":"0000-0001-7964-7402","position":7,"is_corresponding":false},{"id":105317,"name":"Xuping Xie","orcid":"0000-0003-0918-016X","position":8,"is_corresponding":false},{"id":225076,"name":"Steven G. Widen","orcid":"0000-0002-6512-363X","position":9,"is_corresponding":false},{"id":360654,"name":"Hong M. Moulton","orcid":"0000-0002-8095-1513","position":10,"is_corresponding":false},{"id":110494,"name":"Benhur Lee","orcid":"0000-0003-0760-1709","position":11,"is_corresponding":false},{"id":106704,"name":"Jeffrey R. Johnson","orcid":"0000-0002-4221-298X","position":12,"is_corresponding":false},{"id":1363,"name":"Nevan J. Krogan","orcid":"0000-0003-4902-337X","position":13,"is_corresponding":false},{"id":1489,"name":"Adolfo Garcı́a-Sastre","orcid":"0000-0002-6551-1827","position":14,"is_corresponding":false},{"id":38215,"name":"Pei‐Yong Shi","orcid":"0000-0001-5553-1616","position":15,"is_corresponding":false},{"id":105315,"name":"Alexander N. Freiberg","orcid":"0000-0001-8413-8960","position":16,"is_corresponding":false},{"id":107099,"name":"Ricardo Rajsbaum","orcid":"0000-0002-5058-5444","position":17,"is_corresponding":false},{"id":254582,"name":"Adam Hage","orcid":"0000-0001-7668-892X","position":0,"is_corresponding":true}],"reference_count":99,"raw_metadata":null,"created_at":"2026-07-19T00:23:48.622830Z","pmid":"35263596","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":[]}