Ribosome traffic jam in neurodegeneration: decoding hurdles in Huntington disease.

IF 4.1 Q2 CELL BIOLOGY

Cell Stress Pub Date : 2021-05-03 DOI:10.15698/cst2021.06.251

Srinivasa Subramaniam

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引用次数: 1

Abstract

A ribosome typically moves at a particular rate on a given mRNA transcript to decode the nucleic acid information required to synthesize proteins. The speed and directionality of the ribosome movements during mRNA translation are determined by the mRNA sequence and structure and by various decoding factors. However, the molecular mechanisms of this remarkable movement during protein synthesis, or its relevance in brain disorders, remain unknown. Recent studies have indicated that defects in protein synthesis occur in various neurodegenerative diseases, but the mechanistic details are unclear. This is a major problem because identifying the factors that determine protein synthesis defects may offer new avenues for developing therapeutic remedies for currently incurable diseases like neurodegenerative disorders. Based on our recent study (Eshraghi et al., Nat Commun 12(1):1461; doi: 10.1038/s41467-021-21637-y), this short commentary will review the mechanistic understanding of Huntingtin (HTT)-mediated ribosome stalling indicating that central defects in protein synthesis in Huntington disease (HD) are orchestrated by jamming of ribosomes on mRNA transcripts.

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神经退行性疾病中的核糖体阻塞:亨廷顿病的解码障碍。

核糖体通常在给定的mRNA转录本上以特定的速率移动，以解码合成蛋白质所需的核酸信息。mRNA翻译过程中核糖体运动的速度和方向性取决于mRNA的序列和结构以及各种解码因素。然而，在蛋白质合成过程中，这种显著运动的分子机制，或其与脑部疾病的相关性，仍然未知。最近的研究表明，蛋白质合成缺陷发生在各种神经退行性疾病中，但其机制细节尚不清楚。这是一个主要问题，因为确定决定蛋白质合成缺陷的因素可能为开发治疗目前无法治愈的疾病(如神经退行性疾病)的治疗方法提供新的途径。基于我们最近的研究(Eshraghi et al.， Nat comm 12(1):1461;doi: 10.1038/s41467-021-21637-y)，这篇简短的评论将回顾对亨廷顿蛋白(HTT)介导的核糖体停滞的机制理解，表明亨廷顿病(HD)中蛋白质合成的中心缺陷是通过干扰mRNA转录物上的核糖体而精心安排的。

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

Cell Stress Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (miscellaneous)

CiteScore

13.50

自引率

0.00%

发文量

审稿时长

15 weeks

期刊介绍： Cell Stress is an open-access, peer-reviewed journal that is dedicated to publishing highly relevant research in the field of cellular pathology. The journal focuses on advancing our understanding of the molecular, mechanistic, phenotypic, and other critical aspects that underpin cellular dysfunction and disease. It specifically aims to foster cell biology research that is applicable to a range of significant human diseases, including neurodegenerative disorders, myopathies, mitochondriopathies, infectious diseases, cancer, and pathological aging. The scope of Cell Stress is broad, welcoming submissions that represent a spectrum of research from fundamental to translational and clinical studies. The journal is a valuable resource for scientists, educators, and policymakers worldwide, as well as for any individual with an interest in cellular pathology. It serves as a platform for the dissemination of research findings that are instrumental in the investigation, classification, diagnosis, and therapeutic management of major diseases. By being open-access, Cell Stress ensures that its content is freely available to a global audience, thereby promoting international scientific collaboration and accelerating the exchange of knowledge within the research community.