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.
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We thank T. Fujita (Kyoto University) for the luciferase reporter plasmids p-55C1BLuc and p-125Luc; J. Miyazaki (Osaka University) for the pCAGGS vector; A. Miyawaki (RIKEN) for the Venus vector; H. Kida (Hokkaido University) for NDV; A. Iwai, H. Higashi and J. Hamada for technical help; M. Yamane for the purification of human primary CD14+ monocytes; and S. Tamura and T. Moriyama for advice on recombinant protein purification. Supported by the Ministry of Education, Culture, Sports, Science and Technology of Japan (Grant-in-Aid for Young Scientists (A) to S.H., Young Scientists (S) to A.T.) and Scientific Research in Priority Areas (A.T.), IRYO HOJIN SHADAN JIKOKAI (H. Tanaka & N. Takayanagi) (A.T.), the Astellas Foundation for Research on Metabolic Disorders (A.T.), the Kanae Foundation for the Promotion of Medical Science (A.T.), the Kato Memorial Bioscience Foundation (A.T.) and the Yasuda Medical Foundation (A.T.).
The authors declare no competing financial interests.
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Hayakawa, S., Shiratori, S., Yamato, H. et al. ZAPS is a potent stimulator of signaling mediated by the RNA helicase RIG-I during antiviral responses. Nat Immunol 12, 37–44 (2011). https://doi.org/10.1038/ni.1963
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