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

• 成果类型: Article
• 署名作者: Giguere, Sophie; Wang, Xuesong; Huber, Sabrina; Xu, Liling; Warner, John; Weldon, Stephanie R.; Hu, Jennifer; Quynh Anh Phan; Tumang, Katie; Prum, Thavaleak; Ma, Duanduan; Kirsch, Kathrin H.; Nair, Usha; Dedon, Peter; Batista, Facundo D.
• 署名单位: Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Singapore-MIT Alliance for Research & Technology Centre (SMART); Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Massachusetts Institute of Technology (MIT); Swiss Federal Institutes of Technology Domain; ETH Zurich
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11852
• DOI: 10.1126/science.adi1763
• 发表日期: 2024-01-12
• 页码: 205-211
• 关键词: gene-expression; surface-immunoglobulin; adenosine-deaminase; translation; EFFICIENCY; generation; diversity; database; position; LEVEL

摘要

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 naive 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.