Vectorial channeling as a mechanism for translational control by functional prions and condensates
Vectorial channeling as a mechanism for translational control by functional prions and condensates
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DOI：
10.1073/pnas.2115904118
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发表时间：
2021-11-23
影响因子：
11.1
通讯作者：
Wolynes, Peter G.
中科院分区：
文献类型：
--
作者：
Gu, Xinyu;Schafer, Nicholas P.;Wolynes, Peter G.
信使RNA（mRNA）的翻译通过多种RNA结合蛋白调节。RNA结合蛋白的重要部分含有形成功能性朊病毒的朊病毒样结构域。这就提出了朊病毒如何在翻译控制中发挥作用的问题。在突触可塑性和记忆的机制中，朊病毒对树突棘翻译的局部控制已经被调用。我们展示了如何通过扩散和进行性翻译合作，在高度有序的mRNA/朊病毒聚集体，以及在不太有序的mRNA/蛋白质凝聚物，这取决于他们的子结构通道。我们发现，翻译控制的方向，无论是抑制或激活，取决于极性的mRNA分布在mRNA/朊病毒组件，决定是否矢量通道可以提高核糖体的回收。我们的模型还解决了先前已经提出的组件中的底物浓度的变化的影响，以解释翻译控制组件通过引入一个潜在的平均力偏置扩散的核糖体内的组件。从该模型的结果进行了比较与实验数据翻译控制的两个功能RNAbinding朊病毒，CPEB参与记忆和Rim 4参与配子发生。
Translation of messenger RNA (mRNA) is regulated through a diverse set of RNA-binding proteins. A significant fraction of RNA-binding proteins contains prion-like domains which form functional prions. This raises the question of how prions can play a role in translational control. Local control of translation in dendritic spines by prions has been invoked in the mechanism of synaptic plasticity and memory. We show how channeling through diffusion and processive translation cooperate in highly ordered mRNA/prion aggregates as well as in less ordered mRNA/protein condensates depending on their substructure. We show that the direction of translational control, whether it is repressive or activating, depends on the polarity of the mRNA distribution in mRNA/prion assemblies which determines whether vectorial channeling can enhance recycling of ribosomes. Our model also addresses the effect of changes of substrate concentration in assemblies that have been suggested previously to explain translational control by assemblies through the introduction of a potential of mean force biasing diffusion of ribosomes inside the assemblies. The results from the model are compared with the experimental data on translational control by two functional RNAbinding prions, CPEB involved in memory and Rim4 involved in gametogenesis.