被RNase L分裂的转录上的停滞翻译激活了对先天性免疫非常重要的信号传递
Agnes Karasik1, Grant D Jones1, Nicholas R Guydosh2
1NIDDK.
概括
核糖酶L (RNase L) 在感染期间分裂RNA,引发细胞死亡. 分碎的mRNA会阻断核糖体,通过核糖毒应激反应 (RSR) 促进先天免疫力.
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 黎核酶L (RNase L) 是一个内核酶,对先天免疫反应至关重要,在感染期间分裂单链RNA.
- 激活RNase L会触发带毒性应激反应 (RSR),这是一种导致受感染细胞死亡的途径.
- 通过RNase L介导的RNA分裂诱导细胞死亡并使宿主受益的确切机制仍然不完全理解.
研究的目的:
- 研究RNase L的内核酶活动如何触发细胞死亡.
- 为了确定碎片化信使RNA (mRNA) 是否在 рибо毒性应激反应 (RSR) 中起作用.
- 探索核糖体停滞对RNase L.产生的mRNA片段的影响.
主要方法:
- 在RNase L激活后分析mRNA片段的基于纳米孔的长读测序.
- 核糖体概况分析用于识别和量化碎片化mRNA上的核糖体足迹.
- 对核糖体救援因子PELO在RSR中的作用的分析.
主要成果:
- 由RNase L产生的3'mRNA片段被发现被核糖体翻译.
- RNase L激活导致mRNA片段上的RNase L分裂部位的核糖体停滞增加.
- 失去PELO因子加剧了核糖体停滞并增加了RSR.
结论:
- 由RNase L活动引起的碎片化mRNA会导致核糖体停滞.
- 这种在碎片化mRNA上停滞的核糖体通过RSR促进先天性免疫力.
- 这项研究建立了一个新的机制,将RNA碎片化,核糖体动力学和先天免疫信号联系起来.
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