Department of Haematology, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK.
Cambridge Institute for Medical Research, Keith Peters Building, Hills Road, Cambridge CB2 0XY, UK.
Nucleic Acids Res. 2023 May 8;51(8):4043-4054. doi: 10.1093/nar/gkad194.
The chemical modification of ribosomal RNA and proteins is critical for ribosome assembly, for protein synthesis and may drive ribosome specialisation in development and disease. However, the inability to accurately visualise these modifications has limited mechanistic understanding of the role of these modifications in ribosome function. Here we report the 2.15 Å resolution cryo-EM reconstruction of the human 40S ribosomal subunit. We directly visualise post-transcriptional modifications within the 18S rRNA and four post-translational modifications of ribosomal proteins. Additionally, we interpret the solvation shells in the core regions of the 40S ribosomal subunit and reveal how potassium and magnesium ions establish both universally conserved and eukaryote-specific coordination to promote the stabilisation and folding of key ribosomal elements. This work provides unprecedented structural details for the human 40S ribosomal subunit that will serve as an important reference for unravelling the functional role of ribosomal RNA modifications.
核糖体 RNA 和蛋白质的化学修饰对于核糖体组装、蛋白质合成至关重要，并可能在发育和疾病中驱动核糖体的特化。然而，由于无法准确观察这些修饰，因此限制了对这些修饰在核糖体功能中的作用的机制理解。在这里，我们报告了人类 40S 核糖体亚基的 2.15Å 分辨率冷冻电镜重建。我们直接观察到 18S rRNA 内的转录后修饰以及核糖体蛋白的四个翻译后修饰。此外，我们还解释了 40S 核糖体亚基核心区域的溶剂化壳，并揭示了钾离子和镁离子如何建立普遍保守和真核生物特有的配位，以促进关键核糖体元件的稳定和折叠。这项工作为人类 40S 核糖体亚基提供了前所未有的结构细节，将作为揭示核糖体 RNA 修饰功能作用的重要参考。
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