RIG-I 识别了代谢物封顶RNAs 作为信号连接体
Brandon D Schweibenz1,2, Mihai Solotchi1,2, Pranita Hanpude1
1Department of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA.
Nucleic acids research
|June 16, 2023
概括
天生的免疫受体RIG-I识别了代谢物封闭的RNA,刺激了抗病毒反应. 这一发现扩大了我们对RNA传感和RIG-I相关免疫的潜在治疗应用的理解.
科学领域:
- 这是天生的免疫力.
- RNA生物学的RNA生物学
- 分子识别分子识别
背景情况:
- 视网膜酸诱导基因I (RIG-I) 受体检测来自病毒的5'-三酸二链RNAs (5'PPP dsRNA).
- 内源RNAs通常被封闭 (m7G) 和甲基化以避免RIG-I激活和防止自身免疫反应.
- 最近的发现揭示了细胞RNA被NAD+,FAD和dephosphoCoA等代谢物覆盖,但它们与RIG-I的相互作用仍然未知.
研究的目的:
- 为了研究RIG-I是否能识别代谢物封顶RNA.
- 开发一种生产无5'PPP dsRNA污染的代谢物覆盖RNA的方法.
- 阐明RIG-I由代谢物覆盖RNAs激活的机制和细胞后果.
主要方法:
- 在体外转录启动与各种代谢物合成代谢物覆盖RNAs.
- 生物化学测试以评估RIG-I结合亲和力和ATPase活性.
- 细胞信号测试测量天生的抗病毒免疫反应的激活.
主要成果:
- 成功合成了代谢器封顶RNA,没有5'PPP dsRNA污染物.
- 代谢器封顶的RNA对RIG-I具有很高的亲和力,相当于5'PPP dsRNA.
- 这些RNAs在细胞分析中强烈刺激了RIG-I信号传递和先天的抗病毒免疫反应.
结论:
- RIG-I可以识别和激活二酸盐结合,封闭的RNA,在5'端携带体积大的代谢物群.
- 代谢物覆盖RNAs代表了一种新的RIG-I激动剂类,在细胞免疫中具有潜在的作用.
- 这一发现为开发RIG-I向的RNA疗法开辟了道路.
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