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PMID: 21102435 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Nature immunology ·Vol. 12 ·No. 1 ·2011-01-00 ·Pages 37-44

Hayakawa S, Shiratori S, Yamato H, Kameyama T, Kitatsuji C, Kashigi F, Goto S, Kameoka S, Fujikura D, Yamada T, Mizutani T, Kazumata M, Sato M, Tanaka J, Asaka M, Ohba Y, Miyazaki T, Imamura M, Takaoka A

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.

MeSH Terms
Avulavirus Infections/immunology,metabolism DEAD Box Protein 58 DEAD-box RNA Helicases/immunology,metabolism Gene Expression Regulation/genetics,immunology HEK293 Cells Humans Immunity, Innate Interferon Type I/genetics,metabolism Newcastle disease virus/pathogenicity,physiology Orthomyxoviridae/pathogenicity,physiology Orthomyxoviridae Infections/immunology,metabolism Poly I-C/immunology Poly(ADP-ribose) Polymerases/genetics,immunology,metabolism Protein Isoforms/genetics,immunology,metabolism RNA, Small Interfering/genetics RNA-Binding Proteins Receptors, Immunologic Signal Transduction/genetics,immunology Virus Replication/genetics
Chemicals
Interferon Type I Protein Isoforms RNA, Small Interfering RNA-Binding Proteins Receptors, Immunologic ZC3HAV1 protein, human Poly(ADP-ribose) Polymerases DDX58 protein, human DEAD Box Protein 58 DEAD-box RNA Helicases Poly I-C
Authors & Affiliations
19 authors, click to expand affiliations / ORCID
Hayakawa Sumio
Division of Signaling in Cancer and Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
Shiratori Souichi
Yamato Hiroaki
Kameyama Takeshi
Kitatsuji Chihiro
Kashigi Fumi
Goto Showhey
Kameoka Shoichiro
Fujikura Daisuke
Yamada Taisho
Mizutani Tatsuaki
Kazumata Mika
Sato Maiko
Tanaka Junji
Asaka Masahiro
Ohba Yusuke
Miyazaki Tadaaki
Imamura Masahiro
Takaoka Akinori
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Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2916
DOI
10.1038/ni.1963
Published
2011-01-00
Epub
2010-00-21
Pages
37-44
Language
English
Region
United States
NLM ID
100941354
Subset
IM
Corrections
CommentIn
PMID: 21169998
External Links
PubMed source DOI: 10.1038/ni.1963 View journal details
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