核分裂性RNA分裂驱动在天生的免疫反应期间基因表达的变化
Agnes Karasik1, Hernan A Lorenzi2, Andrew V DePass1
1Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Cell reports
|June 1, 2024
概括
病毒感染激活核糖酶L (RNase L),导致RNA分裂. 这触发了抑制病毒的应激反应,但也限制了基因翻译,揭示了复杂的抗病毒机制.
科学领域:
- 分子生物学分子生物学
- 病毒学 病毒学
- 细胞应激反应的应激反应
背景情况:
- 病毒感染激活细胞双链RNA (dsRNA) 传感器.
- 黎核酶L (RNase L) 是一个由dsRNA激活的内核酶,分裂单链RNA.
- RNase L诱导的RNA分裂对基因表达的影响尚不清楚.
研究的目的:
- 研究RNase L介导的RNA分裂如何影响细胞基因表达和抗病毒反应.
- 阐明参与细胞对RNase L活性反应的分子途径.
- 为了比较RNase L与通用内核酶,RNase A.的影响.
主要方法:
- 在细胞中诱导RNase L活性.
- 对RNA碎片化和基因表达的分析.
- 对细胞信号通路的研究 (ZAKα,p38,JNK).
- 评估应激反应基因的转化调节.
- 与RNase A治疗进行比较.
主要成果:
- 由RNase L诱导的RNA分裂通过ZAKα激活了核糖毒性应激反应,可能涉及停滞或碰撞的核糖体.
- 激活的p38和JNK通路促进了诸如编程细胞死亡之类的抗病毒结果.
- 发现RNase L活性限制了应激反应基因的转化.
- 通用内核酶RNase A模仿了RNase L的许多分子表型,表明RNA分裂可以触发抗病毒程序.
结论:
- 广泛的RNA分裂由RNase L启动一个复杂的抗病毒程序,涉及 рибо毒性应激反应和编程细胞死亡.
- RNase L 通过诱导抗病毒反应,同时抑制某些压力基因的转化,发挥双重作用.
- RNA裂变,而不是特定的dsRNA传感,可以成为细胞抗病毒防御机制的足够触发因素.
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