Mu Jianqiang, Wu Cang, Xu Kaiming, Liu Xingang, Fu Yajuan, Zhang Zhen, Yu Jingwei, Xue Chenyang, Wang Zi, Chen Xinmeng, Chen Yanhong, Ou Guangshuo, Liu Zhongmin
Shenzhen Key Laboratory of Biomolecular Assembling and Regulation, School of Life Sciences, Southern University of Science and Technology Shenzhen, 518055 Guangdong, China.
Department of Immunology and Microbiology, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055 Guangdong, China.
Nucleic Acids Res. 2025 Feb 27;53(5). doi: 10.1093/nar/gkaf148.
Adenosine deaminase acting on RNA (ADAR) proteins, which mediate adenosine-to-inosine editing of double-stranded ribonucleic acid (dsRNA) substrates, play essential roles in balancing innate immunity. Using cryogenic electron microscopy, we solved the structure of the Caenorhabditis elegans ADR-2-ADBP-1 complex (stoichiometric ratio, 2:2), which is an asymmetric ADR-2 dimer with one editing site blocked by the other ADR-2. Unexpectedly, dsRNA recruitment triggered dissociation of the ADR-2 dimer, exposing more competent dsRNA editing sites. Furthermore, high dsRNA and protein concentrations caused the formation of liquid-liquid phase-separated puncta, in which significantly greater editing activity was observed, indicating that organizational transitions enable the ADR-2-ADBP-1 complex to perform dsRNA hyper-editing. Our findings suggest that the ADAR editing mechanism adapts to different conditions via conformational reorganization.
作用于RNA的腺苷脱氨酶（ADAR）蛋白可介导双链核糖核酸（dsRNA）底物的腺苷到次黄苷编辑，在平衡先天免疫中发挥重要作用。我们利用低温电子显微镜解析了秀丽隐杆线虫ADR-2-ADBP-1复合物（化学计量比为2:2）的结构，它是一种不对称的ADR-2二聚体，其中一个编辑位点被另一个ADR-2阻断。出乎意料的是，dsRNA的募集引发了ADR-2二聚体的解离，暴露出更多有活性的dsRNA编辑位点。此外，高浓度的dsRNA和蛋白质导致形成液-液相分离的斑点，在其中观察到显著更高的编辑活性，这表明组织转变使ADR-2-ADBP-1复合物能够进行dsRNA超编辑。我们的研究结果表明，ADAR编辑机制通过构象重组适应不同条件。
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