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Article: A novel transcript isoform of STING that sequesters cGAMP and dominantly inhibits innate nucleic acid sensing

TitleA novel transcript isoform of STING that sequesters cGAMP and dominantly inhibits innate nucleic acid sensing
Authors
Issue Date2018
PublisherOxford University Press (OUP): Policy C - Option B. The Journal's web site is located at http://nar.oxfordjournals.org/
Citation
Nucleic Acids Research, 2018, v. 46 n. 8, p. 4054-4071 How to Cite?
AbstractSTING is a core adaptor in innate nucleic acid sensing in mammalian cells, on which different sensing pathways converge to induce type I interferon (IFN) production. Particularly, STING is activated by 2′3′-cGAMP, a cyclic dinucleotide containing mixed phosphodiester linkages and produced by cytoplasmic DNA sensor cGAS. Here, we reported on a novel transcript isoform of STING designated STING-β that dominantly inhibits innate nucleic acid sensing. STING-β without transmembrane domains was widely expressed at low levels in various human tissues and viral induction of STING-β correlated inversely with IFN-β production. The expression of STING-β declined in patients with lupus, in which type I IFNs are commonly overproduced. STING-β suppressed the induction of IFNs, IFN-stimulated genes and other cytokines by various immunostimulatory agents including cyclic dinucleotides, DNA, RNA and viruses, whereas depletion of STING-β showed the opposite effect. STING-β interacted with STING-α and antagonized its antiviral function. STING-β also interacted with TBK1 and prevented it from binding with STING-α, TRIF or other transducers. In addition, STING-β bound to 2′3′-cGAMP and impeded its binding with and activation of STING-α, leading to suppression of IFN-β production. Taken together, STING-β sequesters 2′3′-cGAMP second messenger and other transducer molecules to inhibit innate nucleic acid sensing dominantly.
Persistent Identifierhttp://hdl.handle.net/10722/261085
ISSN
2017 Impact Factor: 11.561
2015 SCImago Journal Rankings: 7.458

 

DC FieldValueLanguage
dc.contributor.authorWang, F-
dc.contributor.authorFung, SY-
dc.contributor.authorGao, W-
dc.contributor.authorDeng, J-
dc.contributor.authorCheng, Y-
dc.contributor.authorChaudhary, V-
dc.contributor.authorYuen, KS-
dc.contributor.authorHo, TH-
dc.contributor.authorChan, CP-
dc.contributor.authorZhang, Y-
dc.contributor.authorKok, KH-
dc.contributor.authorYang, W-
dc.contributor.authorChan, CP-
dc.contributor.authorJin, D-
dc.date.accessioned2018-09-14T08:52:15Z-
dc.date.available2018-09-14T08:52:15Z-
dc.date.issued2018-
dc.identifier.citationNucleic Acids Research, 2018, v. 46 n. 8, p. 4054-4071-
dc.identifier.issn0305-1048-
dc.identifier.urihttp://hdl.handle.net/10722/261085-
dc.description.abstractSTING is a core adaptor in innate nucleic acid sensing in mammalian cells, on which different sensing pathways converge to induce type I interferon (IFN) production. Particularly, STING is activated by 2′3′-cGAMP, a cyclic dinucleotide containing mixed phosphodiester linkages and produced by cytoplasmic DNA sensor cGAS. Here, we reported on a novel transcript isoform of STING designated STING-β that dominantly inhibits innate nucleic acid sensing. STING-β without transmembrane domains was widely expressed at low levels in various human tissues and viral induction of STING-β correlated inversely with IFN-β production. The expression of STING-β declined in patients with lupus, in which type I IFNs are commonly overproduced. STING-β suppressed the induction of IFNs, IFN-stimulated genes and other cytokines by various immunostimulatory agents including cyclic dinucleotides, DNA, RNA and viruses, whereas depletion of STING-β showed the opposite effect. STING-β interacted with STING-α and antagonized its antiviral function. STING-β also interacted with TBK1 and prevented it from binding with STING-α, TRIF or other transducers. In addition, STING-β bound to 2′3′-cGAMP and impeded its binding with and activation of STING-α, leading to suppression of IFN-β production. Taken together, STING-β sequesters 2′3′-cGAMP second messenger and other transducer molecules to inhibit innate nucleic acid sensing dominantly.-
dc.languageeng-
dc.publisherOxford University Press (OUP): Policy C - Option B. The Journal's web site is located at http://nar.oxfordjournals.org/-
dc.relation.ispartofNucleic Acids Research-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleA novel transcript isoform of STING that sequesters cGAMP and dominantly inhibits innate nucleic acid sensing-
dc.typeArticle-
dc.identifier.emailWang, F: wangph@hku.hk-
dc.identifier.emailFung, SY: kittyfsy@connect.hku.hk-
dc.identifier.emailCheng, Y: yuncheng@hku.hk-
dc.identifier.emailYuen, KS: samyuen@hku.hk-
dc.identifier.emailChan, CP: cpchan@hku.hk-
dc.identifier.emailKok, KH: khkok@hku.hk-
dc.identifier.emailYang, W: yangwl@hku.hk-
dc.identifier.emailChan, CP: chancp10@hku.hk-
dc.identifier.emailJin, D: dyjin@hku.hk-
dc.identifier.authorityKok, KH=rp01455-
dc.identifier.authorityYang, W=rp00524-
dc.identifier.authorityChan, CP=rp02031-
dc.identifier.authorityJin, D=rp00452-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1093/nar/gky186-
dc.identifier.hkuros291368-
dc.identifier.volume46-
dc.identifier.issue8-
dc.identifier.spage4054-
dc.identifier.epage4071-
dc.publisher.placeUnited Kingdom-

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