ADAR1 mutation causes ZBP1-dependent immunopathology  

作　　者：Nicholas W Hubbard 

机构地区：[1]不详

出　　处：《四川生理科学杂志》2022年第7期1243-1243,共1页Sichuan Journal of Physiological Sciences

摘　　要：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 species1,2. A point mutation in the sequence encoding the Z-DNA-binding domain (ZBD) of ADAR1 is associated with severe autoinflammatory disease3-5. 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 overt pathology caused by ADAR1 alteration, without fully reversing the underlying inflammatory program caused by this alteration.

关 键 词：ADAR1 ACTIVATION ALTERATION 

分 类 号：Q55[生物学—生物化学]