ADAR1 mutation causes ZBP1-dependent immunopathology.

ABSTRACT: The RNA-editing enzyme ADAR1 is essential for the suppression of innate immune activation and pathology caused by aberrant recognition of self-RNA, a role it carries out by disrupting the duplex structure of endogenous double-stranded RNA species^1,2. A point mutation in the sequence encoding the Z-DNA-binding domain (ZBD) of ADAR1 is associated with severe autoinflammatory disease^3-5. ZBP1 is the only other ZBD-containing mammalian protein⁶, and its activation can trigger both cell death and transcriptional responses through the kinases RIPK1 and RIPK3, and the protease caspase 8 (refs. ^7-9). Here we show that the pathology caused by alteration of the ZBD of ADAR1 is driven by activation of ZBP1. We found that ablation of ZBP1 fully rescued the o

SUBMITTER: Hubbard NW 

PROVIDER: S-EPMC9339495 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature