独立于eIF4E的翻译在很大程度上依赖于eIF3d
Mykola Roiuk1,2,3, Marilena Neff1,2,3, Aurelio A Teleman4,5,6
1German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany.
Nature communications
|August 6, 2024
概括
细胞可以在压力下独立于真核细胞启动因子4E1 (eIF4E1) 转化信使RNA (mRNA). 这种替代途径利用真核启动因子3d (eIF3d) 在eIF4E1失活时促进蛋白质合成.
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 生物化学
背景情况:
- 规范性翻译启动依赖于由真核细胞启动因子4E1 (eIF4E1) 的帽子识别.
- 像低氧和营养缺乏等细胞应激会使mtORC1失活,导致eIF4E1失活.
- 在压力下了解mRNA翻译至关重要,特别是在瘤细胞等环境中.
研究的目的:
- 在压力条件下研究独立于eIF4E1的mRNA翻译机制.
- 为了确定特定的mRNA和参与eIF4E1独立翻译的因素.
主要方法:
- 使用构成性活性4E结合蛋白 (4E-BP) 阻止eIF4E1活动.
- 使用核糖体分析分析分析mRNA翻译效率.
- 使用盖结合试验研究蛋白质-RNA相互作用.
主要成果:
- 当eIF4E1不活跃时,mRNA的一个子集仍然有效地翻译.
- 这些mRNA优先释放eIF4E1并通过其结口袋与真核细胞启动因子3d (eIF3d) 结合.
- eIF3d以独立于eIF4E1的方式促进mRNA翻译.
结论:
- eIF3d-依赖翻译是压力下mRNA翻译的一个重要机制.
- 当正规启动受到损害时,这种途径为蛋白质合成提供了关键的替代方案.
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