The ribosomal RNA of the human protein synthesis machinery comprises numerous chemical modifications that are introduced during ribosome biogenesis. Here we present the 1.9 Å resolution cryo electron microscopy structure of the 80S human ribosome resolving numerous new ribosomal RNA modifications and functionally important ions such as Zn²⁺, K⁺ and Mg²⁺, including their associated individual water molecules. The 2′-O-methylation, pseudo-uridine and base modifications were confirmed by mass spectrometry, resulting in a complete investigation of the >230 sites, many of which could not be addressed previously. They choreograph key interactions within the RNA and at the interface with proteins, including at the ribosomal subunit interfaces of the fully assembled 80S ribosome. Uridine isomerization turns out to be a key mechanism for U–A base pair stabilization in RNA in general. The structural environment of chemical modifications and ions is primordial for the RNA architecture of the mature human ribosome, hence providing a structural framework to address their role in healthy states and in human diseases.

人类蛋白质合成机制的核糖体 RNA 包含在核糖体生物发生过程中引入的许多化学修饰。在这里，我们展示了 80S 人类核糖体的 1.9 Å 分辨率冷冻电子显微镜结构，解析了许多新的核糖体 RNA 修饰和功能上重要的离子，如 Zn ²⁺ 、K ⁺和 Mg ²⁺ ，包括它们相关的单个水分子。通过质谱分析证实了 2'- O-甲基化、假尿苷和碱基修饰，从而对 >230 位点进行了全面研究，其中许多位点以前无法解决。他们设计了 RNA 内以及与蛋白质界面的关键相互作用，包括完全组装的 80S 核糖体的核糖体亚基界面。尿苷异构化被证明是 RNA 中 U-A 碱基对稳定的关键机制。化学修饰和离子的结构环境是成熟人类核糖体RNA结构的原始结构，因此提供了一个结构框架来解决它们在健康状态和人类疾病中的作用。