{"doi":"10.1016/j.celrep.2025.116166","title":"Alternatively spliced isoforms of IRF7 differentially regulate interferon expression to tune response to viral infection","abstract":"Interferon regulatory factor 7 (IRF7) is a master transcriptional regulator of innate immunity. IRF7 binds as a homodimer, or heterodimer with IRF3, to promoters of type I interferons (IFN-Is) to drive their expression, which activates expression of antiviral genes. Here, we demonstrate that alternative splicing of the first intron within the coding region of human IRF7 is regulated across immune tissues and in response to immunologic stimuli. Retention of this intron generates an alternative translation start site, resulting in an N-terminally extended form of the protein (exIRF7) compared to the canonical isoform (cIRF7). We find that exIRF7 has increased dimerization relative to cIRF7, uniquely activates expression of IFN-Is in response to double-stranded RNA (dsRNA) sensing, and controls viral infection to a greater extent than cIRF7. Thus, alternative splicing of IRF7 is a previously unrecognized mechanism by which human cells tune IRF7 function and the IFN response to control immune challenge.","journal":"Cell Reports","year":2025,"id":515197,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9571,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":302510,"name":"Max Ferretti","orcid":"0000-0003-2961-6362","position":1,"is_corresponding":false},{"id":1380015,"name":"Olivia Howard","orcid":null,"position":2,"is_corresponding":false},{"id":348394,"name":"Swechha M. Pokharel","orcid":"0000-0002-9555-5265","position":3,"is_corresponding":false},{"id":1380016,"name":"R.M. McCracken","orcid":null,"position":4,"is_corresponding":false},{"id":1379424,"name":"Simon Boudreault","orcid":"0000-0002-0517-9092","position":5,"is_corresponding":false},{"id":479388,"name":"Mathieu Quesnel-Vallières","orcid":"0000-0001-9945-8123","position":6,"is_corresponding":false},{"id":580363,"name":"Qin Li","orcid":"0000-0002-9797-2636","position":7,"is_corresponding":false},{"id":105475,"name":"Sara Cherry","orcid":"0000-0003-3956-6610","position":8,"is_corresponding":false},{"id":302511,"name":"Kristen W. Lynch","orcid":"0000-0002-0120-8079","position":9,"is_corresponding":false},{"id":1380014,"name":"Asmita Panthi","orcid":null,"position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-19T02:48:39.436300Z","pmid":"40833856","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":[]}