通过tRNA修改优化码翻译速率 保持蛋白质完整性
Danny D Nedialkova1, Sebastian A Leidel2
1Max Planck Research Group for RNA Biology, Max Planck Institute for Molecular Biomedicine, Von-Esmarch-Strasse 54, 48149 Muenster, Germany; Cells-in-Motion Cluster of Excellence, University of Muenster, 48149 Muenster, Germany.
Cell
|June 9, 2015
概括
由修饰的tRNA引起的特定编码子的翻译速度较慢,导致广泛的蛋白质聚合. 恢复tRNA修改可以改善蛋白质平衡,突出显示它们在预防蛋白质毒性压力的作用.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 生物化学 生物化学
背景情况:
- 蛋白质折叠在核糖体翻译过程中开始.
- 核糖体过渡时间可能会影响新生的蛋白质折叠.
- 编码体翻译速率对蛋白质组完整性的影响尚不清楚.
研究的目的:
- 为了研究个体编码体翻译速率如何影响蛋白质折叠和蛋白质组完整性.
- 确定tRNA修饰在调节核糖体过渡和防止蛋白质聚合中的作用.
主要方法:
- 在S. cerevisiae和C. elegans中的核糖体概况.
- 对tRNA抗波动尿素 (U34) 修改的分析.
- 评估蛋白质聚合和蛋白质毒性压力标志物.
主要成果:
- 失去了U34的修饰导致了核糖体在特定的编解子停顿.
- 缺乏U34修饰的细胞显示出蛋白质毒性压力和蛋白质聚合的迹象.
- 过度表达低基调tRNAs挽救了核糖体暂停并恢复了蛋白质平衡.
结论:
- 修改后的U34是一种进化保守的代码解码加速器.
- tRNA修饰在维护蛋白质组完整性方面发挥着至关重要的,以前未被识别的作用.
- 在tRNA修改中的缺陷可以导致蛋白质错误折叠和聚合,导致细胞应激.
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