{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:02:32Z","timestamp":1789448552172,"version":"build-2803163510"},"reference-count":49,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:00:00Z","timestamp":1789171200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hubei Provincial Natural Science Foundation General Project","award":["2024AFB868"],"award-info":[{"award-number":["2024AFB868"]}]},{"DOI":"10.13039\/501100014361","name":"Hubei University of Medicine","doi-asserted-by":"crossref","award":["2024QDJZR001"],"award-info":[{"award-number":["2024QDJZR001"]}],"id":[{"id":"10.13039\/501100014361","id-type":"DOI","asserted-by":"crossref"}]},{"award":["2024QDJZR001"],"award-info":[{"award-number":["2024QDJZR001"]}],"id":[{"id":"https:\/\/ror.org\/01dr2b756","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Emerging evidence has revealed the critical roles of microRNAs (miRNAs) in the regulation of innate immune responses. Nevertheless, it remains poorly understood whether specific miRNAs can directly modulate retinoic acid-inducible gene I (RIG-I), a principal sensor of cytoplasmic viral RNA and a key initiator of antiviral innate immunity. In this study, we identified miR-26a-5p as a potent activator of the innate antiviral immune responses. Notably, this activation operates independently of the canonical miRNA pathways of translational repression and mRNA degradation. Instead, we demonstrated that miR-26a-5p exerts its immunostimulatory effects by specifically binding to the RIG-I receptor. RNA immunoprecipitation and RNA pull-down assays confirmed a direct physical interaction between miR-26a-5p and the RIG-I protein. Subsequent site-directed mutagenesis verified that an AU-rich motif is critical for miR-26a-5p-driven RIG-I activation. Viral challenge experiments demonstrated that miR-26a-5p confers broad-spectrum, RIG-I-dependent antiviral activity against both DNA viruses (herpes simplex virus type 1 and Kaposi\u2019s sarcoma-associated herpesvirus) and RNA viruses (influenza A virus and respiratory syncytial virus). Collectively, our study indicates that miR-26a-5p may serve as a ligand that binds to and activates the RIG-I receptor. This discovery uncovers a previously unrecognized mechanism through which host miRNAs regulate antiviral innate immunity.<\/jats:p>","DOI":"10.3390\/v18091005","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T08:10:23Z","timestamp":1789373423000},"page":"1005","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["miR-26a-5p Activates Antiviral Innate Immunity via Direct Binding and Activation of RIG-I"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8970-4957","authenticated-orcid":false,"given":"Jiasong","family":"Xiong","sequence":"first","affiliation":[{"name":"State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, 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Hubei University of Medicine, Shiyan 442000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Mengke","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Xindi","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Lianzhong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute, Hubei University of Medicine, Shiyan 442000, 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