通过核糖体RNA伪尿化调节翻译
Yu Zhao1, Jay Rai1, Hong Li1,2
1Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, USA.
Science advances
|August 18, 2023
概括
伪尤里丁的修饰对于核糖体的功能至关重要. 它的缺失会导致翻译缺陷,因为它有利于不导向的解码构造,影响蛋白质合成.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 生物化学 生物化学
背景情况:
- 伪乌里丁是一种重要的RNA修饰,存在于各种RNA类型中,包括核糖体RNA (rRNA).
- 伪尿素在核糖体等分子机械中的精确结构和功能作用尚未完全理解,因为未经修改的核糖体结构数据有限.
- 了解这些作用是解读基本生物过程和相关疾病的关键.
研究的目的:
- 为了研究在核糖体中减少伪尿素修饰的结构和功能后果.
- 分析形化对由内部核糖体进入部位 (IRES) 元素介导的翻译启动的影响.
- 阐明由伪尿素损失引起的功能缺陷的分子基础.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 确定了八个高分辨率结构.
- 结构捕获了与多个功能状态中的塔乌拉综合征病毒IRES结合的核糖体.
- 分析的重点是低伪尿化核糖体的相互作用和构造变化.
主要成果:
- 观察到伪尿素介导相互作用的广泛丧失,包括水介导和远程基配对.
- 在真核延长因子2和GTP水解的存在下,假化核糖体采用了一种罕见的,非最佳的解码构造.
- 在保留P位尿素修饰的核糖体中,观察到一种更有利的形状的部分恢复.
结论:
- 这项研究建立了伪尿素修饰的损失和核糖体解码中的功能缺陷之间的直接联系.
- 结构洞察力揭示了伪尿素缺失如何破坏核糖体功能,有利于非生产性状态.
- 这些发现对理解伪乌里丁在其他RNA介导的生物过程和疾病中的作用有影响.
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