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在rRNA上的单个伪乌里丁调节了哺乳动物寄生虫Trypanosoma brucei中的核糖体结构和功能

K Shanmugha Rajan^1,2, Hava Madmoni¹, Anat Bashan²

¹The Mina and Everard Goodman Faculty of Life Sciences and Advanced and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan, 5290002, Israel.

Nature communications

|November 20, 2023

概括

试管体中的伪尿素修饰对于生存至关重要. 改变一个单一的伪尿素部位会影响核糖体组成和蛋白质翻译,这可能有利于寄生虫.

科学领域:

分子寄生虫学分子寄生虫学
在RNA生物学,RNA生物学.
结构生物学结构生物学

背景情况:

试生体是原生虫寄生虫,引起睡眠病,在昆虫和哺乳动物宿主中具有复杂的生命周期.
伪尤里丁 (Ψ) 是一种关键的RNA修饰,影响RNA结构和功能.
特定的伪尿素修饰在三组rRNA中的作用及其功能后果在很大程度上仍未被探索.

研究的目的:

为了研究伪尿素 (Ψ) 修改对核糖体RNA (rRNA) 在Trypanosomes的两个生命阶段的作用.
确定特定的 Ψ 修改对核糖体组成和蛋白质翻译的影响.
阐明 Ψ 修饰介导的核糖体功能变化的结构基础.

主要方法:

利用了四种不同的全基因组方法来研究rRNA伪乌里丁修饰.
采用CRISPR-Cas9基因编辑来淘汰负责指导 Ψ 修改的snoRNA.
分析了核糖体单体组合和蛋白质翻译档案.
确定了高分辨率冷电子显微镜 (cryo-EM) 结构.

主要成果:

在Trypanosomes中,完全淘汰大型rRNA子单元的螺旋69 (H69) 上引导 Ψ 的snoRNAs,被证明是致命的.
在H69上引导 Ψ530 的一个snoRNA 的单一淘汰导致了改变的80S单体组合.
这些核糖体变化特别影响了蛋白质子集的翻译.
一个高分辨率的冷EM结构支持了 Ψ 修饰和核糖体蛋白固体测量之间的相关性.

结论:

在rRNA上的伪尤里丁修饰,特别是在H69上的 Ψ530,对于Trypanosome活力至关重要.
特定的rRNA修改直接影响核糖体组成,并影响蛋白质翻译效率.
改变的rRNA修饰可能会产生核糖体,这些核糖体优先转化有利于状态的蛋白质,帮助寄生虫的适应.

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