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Reference: Maelfait, J, Liverpool, L, Bridgeman, A et al., (2017). Sensing of viral and endogenous RNA by ZBP1/DAI induces necroptosis. EMBO Journal.Citable link to this page:


Sensing of viral and endogenous RNA by ZBP1/DAI induces necroptosis

Abstract: Nucleic acids are potent triggers for innate immunity. Double-stranded DNA and RNA adopt different helical conformations, including the unusual Z-conformation. Z-DNA/RNA is recognised by Z-binding domains (ZBDs), which are present in proteins implicated in antiviral immunity. These include ZBP1 (also known as DAI or DLM-1), which induces necroptosis, an inflammatory form of cell death. Using reconstitution and knock-in models, we report that mutation of key amino acids involved in Z-DNA/RNA binding in ZBP1's ZBDs prevented necroptosis upon infection with mouse cytomegalovirus. Induction of cell death was cell autonomous and required RNA synthesis but not viral DNA replication. Accordingly, ZBP1 directly bound to RNA via its ZBDs. Intact ZBP1-ZBDs were also required for necroptosis triggered by ectopic expression of ZBP1 and caspase blockade, and ZBP1 cross-linked to endogenous RNA These observations show that Z-RNA may constitute a molecular pattern that induces inflammatory cell death upon sensing by ZBP1.

Publication status:PublishedPeer Review status:Peer reviewedVersion:Publisher's version Funder: Medical Research Council   Funder: Wellcome Trust   Notes:Copyright © 2017 The Authors. This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Bibliographic Details

Publisher: EMBO Press

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Journal: EMBO Journalsee more from them

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Issue Date: 17 July 2017Identifiers


Eissn: 1460-2075

Issn: 0261-4189

Uuid: uuid:1765ae72-4412-4348-bfaf-f443f70d755d

Urn: uri:1765ae72-4412-4348-bfaf-f443f70d755d

Pubs-id: pubs:709525 Item Description

Type: journal-article;

Language: eng

Version: Publisher's versionKeywords: DAI ZBP1 Z‐RNA cytomegalovirus necroptosis


Author: Maelfait, J - Oxford, MSD, RDM, Weatherall Insti. of Molecular Medicine fundingEMBO fundingEuropean Commission grantNumberMarie C



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