近日，美国麻省理工学院Facundo D. Batista等研究人员合作发现，抗体的产生依赖于tRNA肌苷的摆动修饰来满足偏向的密码子需求。这一研究成果于2024年1月12日发表在国际顶尖学术期刊《科学》上。

研究人员发现了一种在抗体基因中一致的密码子使用模式。其特征之一是过度使用缺乏基因组编码的沃森-克里克转运核糖核酸（tRNA）的密码子，而依赖于转录后的tRNA修饰肌苷（I34），这种修饰通过摇摆扩大了特定tRNA的解码能力。与初始B细胞相比，抗体分泌细胞的I34含量增加，并更依赖于I34生成蛋白质。

此外，依赖于抗体I34的密码子使用可能会影响B细胞通过调控检查点。这项研究阐明了免疫系统中tRNA池和蛋白质生产之间的关系，对疫苗和治疗用抗体的设计和选择具有重要意义。

据了解，为了提供免疫保护，抗体被大量生产，这给B细胞翻译机制带来了压力。

附：英文原文

Title: Antibody production relies on the tRNA inosine wobble modification to meet biased codon demand

Author: Sophie Giguère, Xuesong Wang, Sabrina Huber, Liling Xu, John Warner, Stephanie R. Weldon, Jennifer Hu, Quynh Anh Phan, Katie Tumang, Thavaleak Prum, Duanduan Ma, Kathrin H. Kirsch, Usha Nair, Peter Dedon, Facundo D. Batista

Issue&Volume: 2024-01-12

Abstract: Antibodies are produced at high rates to provide immunoprotection, which puts pressure on the B cell translational machinery. Here, we identified a pattern of codon usage conserved across antibody genes. One feature thereof is the hyperutilization of codons that lack genome-encoded Watson-Crick transfer RNAs (tRNAs), instead relying on the posttranscriptional tRNA modification inosine (I34), which expands the decoding capacity of specific tRNAs through wobbling. Antibody-secreting cells had increased I34 levels and were more reliant on I34 for protein production than nave B cells. Furthermore, antibody I34-dependent codon usage may influence B cell passage through regulatory checkpoints. Our work elucidates the interface between the tRNA pool and protein production in the immune system and has implications for the design and selection of antibodies for vaccines and therapeutics.

DOI: adi1763

Source: https://www.science.org/doi/10.1126/science.adi1763