Z-nucleic-acid sensing triggers ZBP1-dependent necroptosis and inflammation.

ABSTRACT: The biological function of Z-DNA and Z-RNA, nucleic acid structures with a left-handed double helix, is poorly understood^1-3. Z-DNA-binding protein 1 (ZBP1; also known as DAI or DLM-1) is a nucleic acid sensor that contains two Zα domains that bind Z-DNA^4,5 and Z-RNA^6-8. ZBP1 mediates host defence against some viruses^6,7,9-14 by sensing viral nucleic acids^6,7,10. RIPK1 deficiency, or mutation of its RIP homotypic interaction motif (RHIM), triggers ZBP1-dependent necroptosis and inflammation in mice^15,16. However, the mechanisms that induce ZBP1 activation in the absence of viral infection remain unknown. Here we show that Zα-dependent sensing of endogenous ligands induces ZBP1-mediated perinatal lethality in mice expressing

SUBMITTER: Jiao H 

PROVIDER: S-EPMC7279955 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature