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

作者：Fei Lu, Linghuan Tang, Chun Kim, Dengming Lai, Jinfa Tou, Huipeng Jiao · 发表于：RNA Biology · 年份：2026 · DOI：10.1080/15476286.2026.2691476 · 研究领域：RNA regulation and disease、DNA and Nucleic Acid Chemistry、RNA and protein synthesis mechanisms

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 Zα 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 Zα 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.