Antibody production relies on the tRNA inosine wobble modification to meet biased codon demand.
Publication/Presentation Date
1-12-2024
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 naïve 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.
Volume
383
Issue
6679
First Page
205
Last Page
211
ISSN
1095-9203
Published In/Presented At
Giguère, S., Wang, X., Huber, S., Xu, L., Warner, J., Weldon, S. R., Hu, J., Phan, Q. A., Tumang, K., Prum, T., Ma, D., Kirsch, K. H., Nair, U., Dedon, P., & Batista, F. D. (2024). Antibody production relies on the tRNA inosine wobble modification to meet biased codon demand. Science (New York, N.Y.), 383(6679), 205–211. https://doi.org/10.1126/science.adi1763
Disciplines
Medicine and Health Sciences
PubMedID
38207021
Department(s)
Medical Education
Document Type
Article