Proteostasis regulation through ribosome quality control and no-go-decay.

IF 6.4 2区 生物学 Q1 CELL BIOLOGY Wiley Interdisciplinary Reviews: RNA Pub Date : 2023-11-01 Epub Date: 2023-07-24 DOI:10.1002/wrna.1809
Lokha Ranjani Alagar Boopathy, Emma Beadle, Aitana Garcia-Bueno Rico, Maria Vera
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Abstract

Cell functionality relies on the existing pool of proteins and their folding into functional conformations. This is achieved through the regulation of protein synthesis, which requires error-free mRNAs and ribosomes. Ribosomes are quality control hubs for mRNAs and proteins. Problems during translation elongation slow down the decoding rate, leading to ribosome halting and the eventual collision with the next ribosome. Collided ribosomes form a specific disome structure recognized and solved by ribosome quality control (RQC) mechanisms. RQC pathways orchestrate the degradation of the problematic mRNA by no-go decay and the truncated nascent peptide, the repression of translation initiation, and the recycling of the stalled ribosomes. All these events maintain protein homeostasis and return valuable ribosomes to translation. As such, cell homeostasis and function are maintained at the mRNA level by preventing the production of aberrant or unnecessary proteins. It is becoming evident that the crosstalk between RQC and the protein homeostasis network is vital for cell function, as the absence of RQC components leads to the activation of stress response and neurodegenerative diseases. Here, we review the molecular events of RQC discovered through well-designed stalling reporters. Given the impact of RQC in proteostasis, we discuss the relevance of identifying endogenous mRNA regulated by RQC and their preservation in stress conditions. This article is categorized under: RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms Translation > Regulation.

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通过核糖体质量控制和无衰变来调节蛋白质稳态。
细胞的功能依赖于现有的蛋白质池及其折叠成功能性构象。这是通过调节蛋白质合成来实现的,这需要无错误的mrna和核糖体。核糖体是mrna和蛋白质的质量控制中心。翻译延伸过程中的问题减慢了解码速率,导致核糖体停止并最终与下一个核糖体碰撞。碰撞核糖体形成特定的二体结构,由核糖体质量控制(RQC)机制识别和解决。RQC通路通过no-go衰变和截断新生肽,翻译起始的抑制和停滞核糖体的再循环来协调问题mRNA的降解。所有这些事件都维持了蛋白质的稳态,并使有价值的核糖体恢复翻译。因此,通过防止产生异常或不必要的蛋白质,细胞的稳态和功能维持在mRNA水平。越来越明显的是,RQC和蛋白质稳态网络之间的串扰对细胞功能至关重要,因为RQC成分的缺失会导致应激反应的激活和神经退行性疾病。在这里,我们回顾了通过精心设计的失速记者发现的RQC分子事件。鉴于RQC在蛋白质静止中的影响,我们讨论了鉴定由RQC调节的内源性mRNA及其在应激条件下的保存的相关性。本文分类如下:RNA周转和监视>周转/监视机制翻译>调控。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
14.80
自引率
4.10%
发文量
67
审稿时长
6-12 weeks
期刊介绍: WIREs RNA aims to provide comprehensive, up-to-date, and coherent coverage of this interesting and growing field, providing a framework for both RNA experts and interdisciplinary researchers to not only gain perspective in areas of RNA biology, but to generate new insights and applications as well. Major topics to be covered are: RNA Structure and Dynamics; RNA Evolution and Genomics; RNA-Based Catalysis; RNA Interactions with Proteins and Other Molecules; Translation; RNA Processing; RNA Export/Localization; RNA Turnover and Surveillance; Regulatory RNAs/RNAi/Riboswitches; RNA in Disease and Development; and RNA Methods.
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