被RNase L分裂的转录上的停滞翻译激活了对天生的免疫重要信号传递
bioRxiv : the preprint server for biology
|June 26, 2025
概括
RNase L激活导致碎片化mRNA阻断核糖体,触发核糖毒应激反应 (RSR) 并促进先天免疫力. 这种核糖体停滞对于感染期间的细胞死亡途径至关重要.
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:
- RNase L是一种内核酶,对天生的免疫至关重要,在感染期间分裂单链RNA.
- 激活RNase L会触发核糖毒性应激反应 (RSR),导致细胞死亡.
- 通过RNase L诱导细胞死亡的确切机制仍然不完全理解.
研究的目的:
- 为了研究RNase L激活后的mRNA片段的命运.
- 为了确定核糖体是否在RNase L生成的mRNA片段结束时停滞.
- 阐明核糖体停滞和相关因素在RSR中的作用.
主要方法:
- 基于纳米孔的长读测序来分析mRNA片段.
- 核糖体造型,以识别核糖体足迹和停滞位.
- 对核糖体救援因子PELO在RSR中的作用的分析.
主要成果:
- 激活RNase L导致3'mRNA片段的积累和翻译.
- 观察到核糖体在mRNA片段的RNase L裂变部位停滞.
- 失去PELO加剧了核糖体停滞,并增加了RSR.
结论:
- 分碎的mRNA有助于核糖体停滞,这是RSR的一个关键事件.
- 在RNase L分裂部位的核糖体停滞在先天免疫力中起着重要作用.
- 皮洛作为一个核糖体救援因子,在感染期间调节RSR.
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