The Skaggs Graduate School of Chemical and Biological Sciences, The Scripps Research Institute , La Jolla, CA, USA.
University of Florida-Scripps Biomedical Research , Jupiter, FL, USA.
J Cell Biol. 2023 Apr 3;222(4). doi: 10.1083/jcb.202209115. Epub 2023 Feb 15.
The coordinated integration of ribosomal RNA and protein into two functional ribosomal subunits is safeguarded by quality control checkpoints that ensure ribosomes are correctly assembled and functional before they engage in translation. Quality control is critical in maintaining the integrity of ribosomes and necessary to support healthy cell growth and prevent diseases associated with mistakes in ribosome assembly. Its importance is demonstrated by the finding that bypassing quality control leads to misassembled, malfunctioning ribosomes with altered translation fidelity, which change gene expression and disrupt protein homeostasis. In this review, we outline our understanding of quality control within ribosome synthesis and how failure to enforce quality control contributes to human disease. We first provide a definition of quality control to guide our investigation, briefly present the main assembly steps, and then examine stages of assembly that test ribosome function, establish a pass-fail system to evaluate these functions, and contribute to altered ribosome performance when bypassed, and are thus considered "quality control."
核糖体 RNA 和蛋白质协调整合为两个功能核糖体亚基，由质量控制检查点来保障，该检查点确保核糖体在参与翻译之前正确组装和发挥功能。质量控制对于维持核糖体的完整性至关重要，对于支持健康的细胞生长和预防与核糖体组装错误相关的疾病也是必需的。这一点可以通过以下发现得到证明：绕过质量控制会导致核糖体组装错误、功能失调，从而改变翻译保真度，改变基因表达并破坏蛋白质的平衡。在这篇综述中，我们概述了我们对核糖体合成中质量控制的理解，以及质量控制失败如何导致人类疾病。我们首先提供质量控制的定义来指导我们的研究，简要介绍主要的组装步骤，然后检查组装的各个阶段，这些阶段测试核糖体的功能，建立一个通过/失败的系统来评估这些功能，以及当被绕过时如何导致核糖体性能改变，从而被视为“质量控制”。
