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粉样转化抑制剂Rim4的组装和功能与营养条件相结合

Diana Sm Ottoz¹, Lauren C Tang², Annie E Dyatel¹

¹Department of Genetics and Development, Hammer Health Sciences Center, Columbia University Irving Medical Center, New York, NY, USA.

The EMBO journal

|November 3, 2023

概括

细胞可以使用像Rim4这样的粉样蛋白组件来进行功能控制. 这项研究表明,Rim4组件增强了RNA结合和抑制翻译,在酵母半转化过程中将蛋白质结构与细胞功能联系起来.

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:

粉样蛋白质组合通常与毒性有关,因为它们的结构稳定.
新出现的证据表明,细胞可能利用这些组件来对刺激做出功能调节.
细胞配对组装与环境线索用于功能控制的机制在很大程度上是未知的.

研究的目的:

研究粉样样组合如何在RNA结合蛋白Rim4中赋予新兴功能.
了解细胞如何将Rim4组合与酵母半变异过程中的环境条件联系起来.
阐明Rim4组合在调节基因表达和细胞命运中的作用.

主要方法:

研究了酵母蛋白Rim4,它在介质变化过程中形成翻译抑制组合.
研究了Rim4组装状态及其RNA结合效率之间的关系.
分析了Rim4结合部位位置对翻译抑制的影响.
研究了Rim4组装中内在无序区域 (IDR) 的作用.
评估了Ras/蛋白激酶A信号通路对Rim4组件的影响.

主要成果:

与其单体状态相比,Rim4在其组装,抑制状态中表现出增强的RNA结合,在组装和功能之间建立了直接联系.
转录中的Rim4结合位点的特定位置决定了翻译抑制的有效性,突出了RNA-蛋白质结构架构的重要性.
里姆4组件完全依赖于其本质上无序的区域.
拉斯/蛋白激酶A信号通路抑制Rim4组合,这表明组合与生长和介质输入信号的合机制.

结论:

功能性蛋白质组合可以通过细胞信号通路来调节,以控制基因表达.
细胞可以将Ras/PKA通路等环境刺激与功能性蛋白质组合结合起来,以执行细胞命运决策,例如进入半分裂.
该研究揭示了一种新的机制,其中蛋白质自我组装与RNA结合功能和翻译控制直接相关.

关键词:

RNA结合蛋白质是RNA结合的蛋白质.粉样类组件类似的组件.介质变化 (meiosis) 是一种变质的过程.营养信号的营养信号.蛋白质翻译是蛋白质的翻译.

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