蛋白质合成机械中的一个氧气调节开关
James Uniacke1, Chet E Holterman, Gabriel Lachance
1Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Nature
|June 9, 2012
概括
细胞在氧气不足时合成蛋白质,形成一个新的复合体. 这种复合物,包括HIF-2α,RBM4和eIF4E2,绕过正常的结抑制,使翻译成为可能.
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:
- 蛋白质合成对生命至关重要,由与mRNA帽结合的真核转化启动因子4E (eIF4E) 启动.
- 低氧 (低氧) 抑制了依赖拉巴胺素 (mTOR) 途径的哺乳动物点的甲介导翻译,隔离了eIF4E.
- 替代翻译机制,如内部核糖体进入部位 (IRES),不足以解释缺氧下的蛋白质合成.
研究的目的:
- 研究细胞在缺氧和eIF4E抑制条件下如何合成蛋白质.
- 为了确定新的氧气调节的翻译启动机制.
- 描述缺氧诱导的翻译复合体的组成部分和功能.
主要方法:
- 氧气调节的翻译启动复合物的形成和特征.
- 使用可光激活的核糖核酸增强交联和免疫沉 (PAR-CLIP) 来识别RNA元素.
- 分析复合物对信使RNAs (mRNAs) 的招募.
主要成果:
- 缺氧刺激新型复合物的形成,包括缺氧诱导因子2α (HIF-2α),RNA结合蛋白RBM4和eIF4E2.2.
- PAR-CLIP确定了一种RNA缺氧反应元件 (rHRE),该元件将该复合物招募到特定的mRNA中.
- HIF-2α-RBM4-eIF4E2复合体将mRNA盖在rHRE上结合,使其能够依赖盖的翻译和克服缺氧诱导的抑制.
结论:
- 细胞拥有一个氧气调节的程序,可以切换核心翻译机器.
- 一个新发现的复合体,包括HIF-2α,RBM4和eIF4E2,在缺氧期间调解选择性基依赖蛋白质合成.
- 这种机制使细胞能够保持翻译能力,尽管缺氧和eIF4E抑制.
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