학술논문

Antibody production relies on the tRNA inosine wobble modification to meet biased codon demand.
Document Type
Article
Source
Science. 1/12/2024, Vol. 383 Issue 6679, p205-211. 7p. 4 Diagrams.
Subject
*TRANSFER RNA
*ANTIBODY formation
*PROTEIN expression
*B cells
*INOSINE
Language
ISSN
0036-8075
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. [ABSTRACT FROM AUTHOR]