Miyauchi Kenjyo, Kimura Satoshi, Akiyama Naho, Inoue Kazuki, Ishiguro Kensuke, Vu Thien-Son, Srisuknimit Veerasak, Koyama Kenta, Hayashi Gosuke, Soma Akiko, Nagao Asuteka, Shirouzu Mikako, Okamoto Akimitsu, Waldor Matthew K, Suzuki Tsutomu
Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan.
Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA.
Nat Chem Biol. 2025 Apr;21(4):522-531. doi: 10.1038/s41589-024-01726-x. Epub 2024 Sep 19.
Modified tRNA anticodons are critical for proper mRNA translation during protein synthesis. It is generally thought that almost all bacterial tRNAs use a modified cytidine-lysidine (L)-at the first position (34) of the anticodon to decipher the AUA codon as isoleucine (Ile). Here we report that tRNAs from plant organelles and a subset of bacteria contain a new cytidine derivative, designated 2-aminovaleramididine (avaC). Like L34, avaC34 governs both Ile-charging ability and AUA decoding. Cryo-electron microscopy structural analyses revealed molecular details of codon recognition by avaC34 with a specific interaction between its terminal amide group and an mRNA residue 3'-adjacent to the AUA codon. These findings reveal the evolutionary variation of an essential tRNA modification and demonstrate the molecular basis of AUA decoding mediated by a unique tRNA modification.
修饰的tRNA反密码子在蛋白质合成过程中对正确的mRNA翻译至关重要。一般认为，几乎所有细菌的tRNA在反密码子的第一位（34位）使用修饰的胞嘧啶-赖氨酸（L），将AUA密码子解读为异亮氨酸（Ile）。在此，我们报告来自植物细胞器和一部分细菌的tRNA含有一种新的胞嘧啶衍生物，命名为2-氨基戊脒（avaC）。与L34一样，avaC34既控制异亮氨酸负载能力，也控制AUA解码。冷冻电子显微镜结构分析揭示了avaC34识别密码子的分子细节，其末端酰胺基团与AUA密码子3'相邻的mRNA残基之间存在特定相互作用。这些发现揭示了一种重要tRNA修饰的进化变异，并证明了由独特tRNA修饰介导的AUA解码的分子基础。
