Biological consequences of Z-nucleic acid sensing by ZBP1 and ADAR1

초록

Since their discovery, Z-nucleic acids (Z-NAs), which adopt a left-handed double helical conformation, have puzzled researchers regarding their physiological functions. These unusual nucleic acids are recognized by proteins containing Z alpha domains, particularly Z-DNA binding protein 1 (ZBP1) and adenosine deaminase acting on RNA 1 (ADAR1). Utilizing mouse genetics with knockout models and site-specific Z alpha domain mutations, scientists have revealed that Z-NAs serve as critical regulators of programmed cell death, inflammation, antiviral immunity, and anti-tumour responses. This review systematically examines mechanistic insights from Zbp1- and Adar1-mutant models, illuminating how Z-NAs play a dual role as essential triggers of host defence and as potential drivers of autoinflammatory diseases.

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