Modified tRNA anticodons are critical for proper mRNA translation during protein synthesis. It is generally thought that almost all bacterial tRNAs^Ile 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^Ile from plant organelles and a subset of bacteria contain a new cytidine derivative, designated 2-aminovaleramididine (ava²C). Like L34, ava²C34 governs both Ile-charging ability and AUA decoding. Cryo-electron microscopy structural analyses revealed molecular details of codon recognition by ava²C34 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 反密码子对于蛋白质合成过程中 mRNA 的正确翻译至关重要。一般认为，几乎所有细菌 tRNA ^Ile在反密码子的第一个位置 (34) 都使用修饰的胞苷 - 赖氨酸 (L)，将 AUA 密码子破译为​​异亮氨酸 (Ile)。在这里，我们报道来自植物细胞器和细菌子集的 tRNA ^Ile含有一种新的胞苷衍生物，称为 2-氨基戊脒 (ava ² C)。与 L34 一样，ava ² C34 控制 Ile 充电能力和 AUA 解码。冷冻电镜结构分析揭示了 ava ² C34 密码子识别的分子细节，其末端酰胺基团与 AUA 密码子 3' 附近的 mRNA 残基之间存在特异性相互作用。这些发现揭示了必需 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。