title: Dual effects of duplex RNA harboring 5'-terminal triphosphate on gene silencing and RIG-I mediated innate immune response.
abstract: Duplex RNA harboring the 5'-terminal triphosphate RNA is hypothesized to not only execute selective gene silencing via RNA interference, but also induce type I interferon (IFN) through activation of the retinoic acid inducible gene I (RIG-I). We evaluated gene silencing efficacy of the shRNA containing 5'-triphosphate (3p-shRNA) targeting the hepatitis C virus (HCV) RNA genome in hepatic cells. Gene silencing efficacy of the 3p-shRNA was diminished due to the presence of the 5'-triphosphate moiety in shRNA, whereas the shRNA counterpart without 5'-triphosphate (HO-shRNA) showed a strong antiviral activity without significant induction of type I IFN in the cells. 3p-shRNA was observed to be a better activator of the RIG-I signaling than the HO-shRNA with an elevated induction of type I IFN in cells that express RIG-I. Taken together, we suggest that competition for the duplex RNA bearing 5'-triphosphate between RIG-I and RNA interference factors may compromise efficacy of selective gene silencing.
authors.affiliation: Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Si Eun
authors.initials: SE
authors.lastname: Baek
authors.affiliation: Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Hyoseon
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Kyung Bo
authors.initials: KB
authors.lastname: Kim
authors.affiliation: Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Soojin
authors.initials: S
authors.lastname: Yoon
authors.affiliation: Department of Life Sciences, University of Seoul, Seoul 130-743, Republic of Korea.
authors.forename: Jungwoo
authors.initials: J
authors.lastname: Choe
authors.affiliation: College of Pharmacy, Ajou University, Suwon 443-749, Republic of Korea.
authors.forename: Wonhee
authors.initials: W
authors.lastname: Suh
authors.affiliation: Department of Bio and Nanochemistry, Kookmin University, Seoul 136-702, Republic of Korea.
authors.forename: Yong-Joo
authors.initials: YJ
authors.lastname: Jeong
authors.affiliation: Department of Internal Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul 143-701, Republic of Korea; Department of Internal Medicine, School of Medicine, Kangwon National University, Chuncheon 200-701, Republic of Korea.
authors.forename: Yo Han
authors.initials: YH
authors.lastname: Cho
authors.affiliation: Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea. Electronic address: kimde@konkuk.ac.kr.
authors.forename: Dong-Eun
authors.initials: DE
authors.lastname: Kim
mesh_terms: D045744:Cell Line, Tumor; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D020868:Gene Silencing; D016679:Genome, Viral / Q000235:genetics; D016174:Hepacivirus / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D007370:Interferon Type I / Q000276:immunology; D009690:Nucleic Acid Conformation; D011122:Polyphosphates / Q000737:chemistry*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000235:genetics; D011971:Receptors, Immunologic
chemical_list: D007370:Interferon Type I; D011122:Polyphosphates; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; C005692:triphosphoric acid
keywords: 5′-Terminal triphosphate; Duplex RNA; Innate immune response; Retinoic acid inducible gene I (RIG-I)