端粒重复含有RNA的G-四重复触发ZBP1介导的细胞死亡
Geng Qin1,2,3, Chuanqi Zhao1,2, Chengming Gao4
1Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, PR China.
Nature communications
|February 23, 2026
概括
Z-DNA结合蛋白1-S (ZBP1-S) 感知了端粒重复含有RNA (TERRA) 中的G四重复,从而触发了炎症细胞死亡. 特定于G4的配体阻断这种相互作用,抑制ZBP1-S介导的免疫信号传递.
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 遗传学 是一个遗传学.
背景情况:
- Z-DNA结合蛋白1 (ZBP1) 是一种核酸传感器,参与炎症性细胞死亡.
- 截断的ZBP1-S异型感知到端粒重复含有RNA (TERRA),激活天生的免疫力.
- 对于ZBP1-S感知TERRA的确切机制尚不完全理解.
研究的目的:
- 为了阐明ZBP1-S感知TERRA的机制.
- 调查G四复合体 (G4s) 在ZBP1-S激活中的作用.
- 探索针对ZBP1-S-TERRA相互作用的潜在治疗策略.
主要方法:
- 生物化学分析以证明ZBP1-S与TERRA G4结构的直接结合.
- 寡合化试验用于评估ZBP1-S在G4结合时的形状变化.
- 作为对ZBP1-S和TERRA G4s的反应,干扰素信号通路激活测定.
- 使用G4特异性配体阻止ZBP1-S-TERRA相互作用的抑制研究.
主要成果:
- ZBP1-S直接与TERRA内部的G-四重复结构结合.
- 结合TERRA G4s诱导ZBP1-S的寡合化.
- ZBP1-S 寡合化导致诱导炎症性细胞死亡.
- 特定于G4的配体有效地与ZBP1-S竞争TERRA结合,并抑制ZBP1-S介导的干扰素信号传递.
结论:
- 作为主要的传感机制,ZBP1-S识别并与TERRA中的G-四重复结构结合.
- 这种相互作用触发了ZBP1-S寡合化和随后的炎症细胞死亡.
- 用特定的配体向TERRA G4s提供了一个潜在的治疗方法来调节ZBP1-S驱动的炎症.
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