冷冻电镜结构揭示RNA修饰对核糖体组装和翻译的影响
张云阳，高 宁∗
（１．北京大学生命科学学院；2．国家生物医学影像中心， 北京 100871）
摘 要 RNA修饰广泛存在于所有主要RNA类别（包括信使RNA、转运RNA、核糖体RNA）中，核糖体RNA (rRNA) 因其刚性的结构，为使用冷冻电镜（Cryo-EM）技术探讨RNA修饰的结构与功能之间的关系提供了一个理想的平台。rRNA的修饰主要包括甲基化修饰和假尿嘧啶化修饰，这些修饰不仅扩展了rRNA的化学和拓扑属性，还显著影响核糖体亚基的组装和翻译的效率。特别是在肽基转移酶中心（PTC）的A-loop区域，rRNA修饰通过影响tRNA的选择和肽链的延伸，显著提高蛋白质合成效率。冷冻电镜结构分析在揭示RNA修饰对核糖体组装和翻译的影响方面发挥了重要作用。本综述基于生物化学数据和冷冻电镜结构，详细探讨了rRNA修饰的生物学重要性，并特别强调了A-loop在PTC中的功能和其修饰对核糖体性能的影响。研究表明，A-loop的修饰在原核细胞、真核细胞中显示出高度的保守性，这反映了其在确保蛋白质正确延伸中的关键作用。rRNA的修饰主要由RNA介导，但也包括由独立的甲基转移酶（如RrmJ/Spb1家族）执行的2′-O-甲基化，RrmJ/Spb1家族蛋白识别组装中的核糖体并对A-loop进行修饰，成为核糖体组装过程中关键的质量控制检查点，本综述还分析了RrmJ/Spb1功能缺失或者突变对核糖体组装产生的严重影响。
关键词 冷冻电镜；核糖体RNA修饰；rRNA甲基化；肽基转移酶中心（PTC）；A-loop；核糖体组装；翻译效率
中图分类号：Q336；Q518.2；Q522+.3 文献标识码：ADoi:10.3969/j.issn.1000-6281.2025.01.013
Cryo-EM structures reveal the impact of RNA modifications on ribosome assembly and translation
ZHANG Yunyang，GAO Ning*
（1.School of Life Sciences, Peking University, Beijing 100871；2.National Biomedical Imaging Center, Beijing 100871, China）
Abstract RNA modifications are widespread in all major types of RNA, and ribosomal RNA (rRNA), due to its rigid structure, provides an ideal platform to explore the relationship between RNA modifications and their structural and functional roles using Cryo-electron microscopy (Cryo-EM). rRNA modifications, primarily methylation and pseudouridylation, not only expand the chemical and topological properties of rRNA but also significantly affect ribosomal subunit assembly and translation efficiency. In particular, in the A-loop region of the peptidyl transferase center (PTC), rRNA modifications enhance the efficiency of protein synthesis by influencing tRNA selection and peptide chain elongation. Cryo-EM structural analysis plays a critical role in revealing the effects of RNA modifications on ribosome assembly and translation. This review, based on biochemical studies and cryo-EM structures, provides a detailed discussion of the biological significance of rRNA modifications, with a focus on the A-loop in the PTC and how its modifications affect ribosome performance. Studies have shown that A-loop modifications are highly conserved across prokaryotic and eukaryotic cells, reflecting their critical role in ensuring accurate expression of genetic information and proper peptide elongation. rRNA modifications are primarily mediated by RNA but also include 2'-O-methylation performed by independent methyltransferases, such as the RrmJ/Spb1 family. These proteins recognize ribosomes during assembly and modify the A-loop, serving as important quality control checkpoints in ribosome assembly. This review also analyzes the severe effects of RrmJ/Spb1 depletion or mutation on ribosome assembly.
Keywords Cryo-electron microscopy；ribosomal RNA modifications；rRNA methylation；peptidyl transferase center (PTC)；A-loop；ribosome assembly；translation efficiency
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