通过RIG-I反来自我识别可诱导宿主 lncRNA 限制先天免疫反应
Minghong Jiang1, Shikun Zhang1, Zongheng Yang1
1National Key Laboratory of Medical Molecular Biology, Department of Immunology & Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100005, China.
Cell
|May 1, 2018
概括
一个新发现的宿主RNA, lnc-Lsm3b, 作为一个诱来抑制RIG-I传感器, 关闭抗病毒反应. 这一发现揭示了一种新的免疫调节机制,
科学领域:
- 免疫学
- 分子生物学
- 核糖核酸生物学
背景情况:
- RIG- I蛋白质是检测病毒RNA和启动抗病毒免疫反应的关键传感器,包括I型干扰素 (IFN) 的产生.
- 调节先天免疫反应对于维持平衡和预防过度炎症至关重要.
研究的目的:
- 确定调节RIG-I天生的免疫路径的宿主因素.
- 阐明Inc-Lsm3b调节RIG-I活动和先天免疫的机制.
主要方法:
- 识别和表征IFN诱导的长非编码RNA (lncRNAs).
- 生物化学测定以评估Inc-Lsm3b与RIG-I的结合.
- 在Inc-Lsm3b结合时对RIG-I形状变化和下游信号的分析.
- 对Inc-Lsm3b进行结构分析,以确定RIG-I相互作用的关键特征.
主要成果:
- 鉴定了一种源自宿主的IFN诱导的lncRNA,称为lnc-Lsm3b.
- lnc-Lsm3b与病毒RNA竞争结合RIG-I单体.
- lnc-Lsm3b的结合抑制了RIG-I的形状变化,阻止了下游信号和终止了I型IFN的产生.
- 对于RIG-I结合和抑制,Inc-Lsm3b的特定结构特征,包括多价值基因和长茎结构,至关重要.
结论:
- lnc-Lsm3b作为一个分子诱,与RIG-I结合并限制抗病毒反应的持续时间.
- 这代表了免疫调节中的非正规自我识别机制.
- 通过积极控制先天免疫信号, lnc- Lsm3b 在维持免疫平衡方面发挥作用.
- 这些发现表明Inc-Lsm3b在治疗炎症疾病方面的潜在治疗应用.
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