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: Sumio Hayakawa, 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
• Journal: Nature immunology (Nat Immunol) Vol. 12 Issue 1 Pg. 37-44 (Jan 2011) ISSN: 1529-2916 [Electronic] United States
• PMID: 21102435 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interferon Type I
• Protein Isoforms
• RNA, Small Interfering
• RNA-Binding Proteins
• Receptors, Immunologic
• ZC3HAV1 protein, human
• Poly(ADP-ribose) Polymerases
• RIGI protein, human
• DEAD Box Protein 58
• DEAD-box RNA Helicases
• Poly I-C

Topics

• 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)