eIF5B的内在无序区域刺激IRES的使用,并核化生物颗粒形成
Meghan T Harris1, Michael T Marr1
1Department of Biology and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02453, USA.
Cell reports
|October 20, 2023
概括
细胞压力通过内部核糖体进入点 (IRES) 激活翻译启动. 细胞启动因子5B (eIF5B) 和其N端区域促进IRES活动,甚至形成压力触发的颗粒.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生化学
背景情况:
- 细胞激活应激反应通路以生存不利条件,经常抑制全球上限依赖转化.
- 基本的转录通过使用替代的翻译启动方法来逃避这种抑制,例如内部核糖体进入点 (IRES).
- 细胞IRES在关键应激反应转录中发现,包括胰岛素受体 (Insr) 和胰岛素样生长因子1受体 (Igf1r).
研究的目的:
- 研究5B真核启动因子 (eIF5B) 在促进细胞应激期间的IRES活动中的作用.
- 阐明eIF5B影响IRES介导翻译的机制.
- 确定eIF5B是否可以形成专门增强IRES功能的结构.
主要方法:
- 研究了eIF5B对Insr,Igf1r和C型肝炎病毒IRES活动的影响.
- 使用生物化学分析来检查eIF5B与IRES元素相互作用的机制.
- 在细胞应激条件下观察到由eIF5B的N端区域驱动的细胞质颗粒的形成.
主要成果:
- eIF5B优先促进Insr,Igf1r和C型肝炎病毒的IRES活动.
- 这种提升通过一种依赖eIF5B的充电和无序N终端的非正规机制发生.
- eIF5B的N端区域可以驱动细胞质颗粒的形成,这是由细胞应激引发的,足以特别促进IRES活动.
结论:
- eIF5B在促进细胞应激期间的IRES介导翻译方面发挥着至关重要的作用.
- eIF5B的N端区域对于这个功能至关重要,可以调解压力诱导的颗粒形成.
- 这些发现揭示了一种通过eIF5B依赖IRES活动调节压力反应基因翻译的新机制.
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