ADAR1 averts fatal type I interferon induction by ZBP1.

ABSTRACT: Mutations of the ADAR1 gene encoding an RNA deaminase cause severe diseases associated with chronic activation of type I interferon (IFN) responses, including Aicardi-Goutières syndrome and bilateral striatal necrosis^1-3. The IFN-inducible p150 isoform of ADAR1 contains a Zα domain that recognizes RNA with an alternative left-handed double-helix structure, termed Z-RNA^4,5. Hemizygous ADAR1 mutations in the Zα domain cause type I IFN-mediated pathologies in humans^2,3 and mice^6-8; however, it remains unclear how the interaction of ADAR1 with Z-RNA prevents IFN activation. Here we show that Z-DNA-binding protein 1 (ZBP1), the only other protein in mammals known to harbour Zα domains⁹, promotes type I IFN activation and fatal pathology in

SUBMITTER: Jiao H 

PROVIDER: S-EPMC9329096 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature