ZAPS is a potent stimulator of signaling mediated by the RNA helicase RIG-I during antiviral responses

  • Nat Immunol. 2011 Jan;12(1):37-44. doi: 10.1038/ni.1963.
Sumio Hayakawa  1 ,  Souichi Shiratori ,  Hiroaki Yamato ,  Takeshi Kameyama ,  Chihiro Kitatsuji ,  Fumi Kashigi ,  Showhey Goto ,  Shoichiro Kameoka ,  Daisuke Fujikura ,  Taisho Yamada ,  Tatsuaki Mizutani ,  Mika Kazumata ,  Maiko Sato ,  Junji Tanaka ,  Masahiro Asaka ,  Yusuke Ohba ,  Tadaaki Miyazaki ,  Masahiro Imamura ,  Akinori Takaoka
Affiliations
  • 1. Division of Signaling in Cancer and Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
PMID: 21102435 DOI: 10.1038/ni.1963
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.