title: ZAPS is a potent stimulator of signaling mediated by the RNA helicase RIG-I during antiviral responses.
abstract: The poly(ADP-ribose) polymerases (PARPs) participate in many biological and pathological processes. Here we report that the PARP-13 shorter isoform (ZAPS), rather than the full-length protein (ZAP), was selectively induced by 5'-triphosphate-modified RNA (3pRNA) and functioned as a potent stimulator of interferon responses in human cells mediated by the RNA helicase RIG-I. ZAPS associated with RIG-I to promote the oligomerization and ATPase activity of RIG-I, which led to robust activation of IRF3 and NF-κB transcription factors. Disruption of the gene encoding ZAPS resulted in impaired induction of interferon-α (IFN-α), IFN-β and other cytokines after viral infection. These results indicate that ZAPS is a key regulator of RIG-I signaling during the innate antiviral immune response, which suggests its possible use as a therapeutic target for viral control.
authors.affiliation: Division of Signaling in Cancer and Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Sumio
authors.initials: S
authors.lastname: Hayakawa
authors.forename: Souichi
authors.initials: S
authors.lastname: Shiratori
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yamato
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kameyama
authors.forename: Chihiro
authors.initials: C
authors.lastname: Kitatsuji
authors.forename: Fumi
authors.initials: F
authors.lastname: Kashigi
authors.forename: Showhey
authors.initials: S
authors.lastname: Goto
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Kameoka
authors.forename: Daisuke
authors.initials: D
authors.lastname: Fujikura
authors.forename: Taisho
authors.initials: T
authors.lastname: Yamada
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Mizutani
authors.forename: Mika
authors.initials: M
authors.lastname: Kazumata
authors.forename: Maiko
authors.initials: M
authors.lastname: Sato
authors.forename: Junji
authors.initials: J
authors.lastname: Tanaka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Asaka
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ohba
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Imamura
authors.forename: Akinori
authors.initials: A
authors.lastname: Takaoka
mesh_terms: D045463:Avulavirus Infections / Q000276:immunology / Q000378:metabolism*; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism; D009522:Newcastle disease virus / Q000472:pathogenicity / Q000502:physiology*; D009975:Orthomyxoviridae / Q000472:pathogenicity / Q000502:physiology*; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000378:metabolism*; D011070:Poly I-C / Q000276:immunology; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins; D011971:Receptors, Immunologic; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D014779:Virus Replication / Q000235:genetics
chemical_list: D007370:Interferon Type I; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D011971:Receptors, Immunologic; C527496:ZC3HAV1 protein, human; D011065:Poly(ADP-ribose) Polymerases; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D011070:Poly I-C