在mTORC1抑制过程中,eIF4A1增强了LARP1介导的翻译抑制
Yuichi Shichino1, Tomokazu Yamaguchi2,3, Kazuhiro Kashiwagi4
1RNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Wako, Japan. yuichi.shichino@riken.jp.
Nature structural & molecular biology
|May 21, 2024
概括
细胞翻译启动因子4A1 (eIF4A1) 令人惊的是增强了翻译抑制,特别是对于TOPmRNA,当mTORC1信号被抑制时. 这一发现揭示了关键翻译激活剂的新型镇压作用.
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:
- 细胞翻译启动因子4A (eIF4A) 是一个DEAD-boxRNA结合蛋白,对翻译启动至关重要.
- 虽然以促进翻译而闻名,但eIF4A的各种功能,包括潜在的镇压作用,尚未完全理解.
研究的目的:
- 调查eIF4A1在转化调节中的作用,特别是在抑制拉巴胺素复合物1 (mTORC1) 的机械性标期间.
- 阐明eIF4A1在特定细胞条件下调节蛋白质合成的机制.
主要方法:
- 接着是测序以识别eIF4A1结合的mRNAs.
- 核糖体造型,以评估翻译效率.
- 对eIF4A1,LARP1和TOPmRNA之间的相互作用进行分析.
主要成果:
- eIF4A1优先与具有终端寡聚胺 (TOP) 基因的mRNA结合,这些基因在mTORC1抑制时被转化抑制.
- 删除EIF4A1减弱了mTORC1失活后TOP mRNA翻译的抑制.
- eIF4A1增强了TOP mRNA和LARP1之间的相互作用,导致翻译抑制增加.
结论:
- eIF4A1在转化抑制中发挥着重要作用,特别是在TOP mRNA中,作为对mTORC1抑制的反应.
- 这项研究强调了eIF4A1的多模式功能,证明了它通过与LARP1.1等抑制性伙伴的相互作用来作为抑制剂的能力.
- 提供了一个一般翻译激活器在特定环境中具有压制性功能的新奇例子.
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