{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T15:15:30Z","timestamp":1781795730109,"version":"3.54.5"},"reference-count":32,"publisher":"National Academy of Sciences","issue":"29","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,7,21]]},"abstract":"<jats:p>The ATPase retinoid acid-inducible gene (RIG)-I senses viral RNA in the cytoplasm of infected cells and subsequently activates cellular antiviral defense mechanisms. RIG-I recognizes molecular structures that discriminate viral from host RNA. Here, we show that RIG-I ligands require base-paired structures in conjunction with a free 5\u2032-triphosphate to trigger antiviral signaling. Hitherto unavailable chemically synthesized 5\u2032-triphosphate RNA ligands do not trigger RIG-I-dependent IFN production in cells, and they are unable to trigger the ATPase activity of RIG-I without a base-paired stretch. Consistently, immunostimulatory RNA from cells infected with a virus recognized by RIG-I is sensitive to double-strand, but not single-strand, specific RNases. In vitro, base-paired stretches and the 5\u2032-triphosphate bind to distinct sites of RIG-I and synergize to trigger the induction of signaling competent RIG-I multimers. Strengthening our model of a bipartite molecular pattern for RIG-I activation, we show that the activity of supposedly \u201csingle-stranded\u201d 5\u2032-triphosphate RNAs generated by in vitro transcription depends on extended and base-paired by-products inadvertently, but commonly, produced by this method. Together, our findings accurately define a minimal molecular pattern sufficient to activate RIG-I that can be found in viral genomes or transcripts.<\/jats:p>","DOI":"10.1073\/pnas.0900971106","type":"journal-article","created":{"date-parts":[[2009,7,2]],"date-time":"2009-07-02T22:36:04Z","timestamp":1246574164000},"page":"12067-12072","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":351,"title":["5\u2032-triphosphate RNA requires base-paired structures to activate antiviral signaling via RIG-I"],"prefix":"10.1073","volume":"106","author":[{"given":"Andreas","family":"Schmidt","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, Ludwig-Maximilian University Munich, 80336 Munich, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Schwerd","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, Ludwig-Maximilian University Munich, 80336 Munich, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Hamm","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, Ludwig-Maximilian University Munich, 80336 Munich, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes C.","family":"Hellmuth","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, Ludwig-Maximilian University Munich, 80336 Munich, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Cui","sequence":"additional","affiliation":[{"name":"Center for Integrated Protein Sciences, Department of Chemistry and Biochemistry, Gene Center, Ludwig-Maximilian University Munich, 81377 Munich, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Wenzel","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, Ludwig-Maximilian University Munich, 80336 Munich, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska S.","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, Ludwig-Maximilian University Munich, 80336 Munich, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Cecile","family":"Michallet","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Besch","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl-Peter","family":"Hopfner","sequence":"additional","affiliation":[{"name":"Center for Integrated Protein Sciences, Department of Chemistry and Biochemistry, Gene Center, Ludwig-Maximilian University Munich, 81377 Munich, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Endres","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, Ludwig-Maximilian University Munich, 80336 Munich, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Rothenfusser","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, Ludwig-Maximilian University Munich, 80336 Munich, Germany;"},{"name":"Section Gastroenterology and Endocrinology, Medizinische Klinik Innenstadt, Ludwig-Maximilian University Munich, 80337 Munich, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,7,21]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.02.015"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0407639101"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.8.5260"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1087"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601314"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.5.2689-2699.2005"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2005.12.003"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt940"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1132505"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1132998"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.10.032"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.11.028"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06042"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20080091"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07106"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1093616"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1191"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.15.6972"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1033.2003.03510.x"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb00329.x"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg595"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04734"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.80.10.5059-5064.2006"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00724.x"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(77)90130-1"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1999.9871"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0603082103"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.5.2851"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkl540"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M806219200"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0000279"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1168352"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0900971106","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T16:57:13Z","timestamp":1653325033000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0900971106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,7,21]]},"references-count":32,"journal-issue":{"issue":"29","published-print":{"date-parts":[[2009,7,21]]}},"alternative-id":["10.1073\/pnas.0900971106"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0900971106","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1162804.624407","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,7,21]]},"assertion":[{"value":"2009-01-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-07-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}