• Availability of Charged tRNAs...

Treffer: Availability of Charged tRNAs Drives Maximal Protein Synthesis at Intermediate Levels of Codon Usage Bias.

Title:
Availability of Charged tRNAs Drives Maximal Protein Synthesis at Intermediate Levels of Codon Usage Bias.
Authors:
Hill AM; Department of Integrative Biology, The University of Texas at Austin, Austin, Texas, USA., To K; Department of Integrative Biology, The University of Texas at Austin, Austin, Texas, USA., Wilke CO; Department of Integrative Biology, The University of Texas at Austin, Austin, Texas, USA. wilke@austin.utexas.edu.
Source:
Bulletin of mathematical biology [Bull Math Biol] 2026 Jan 14; Vol. 88 (2), pp. 16. Date of Electronic Publication: 2026 Jan 14.
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: Springer Country of Publication: United States NLM ID: 0401404 Publication Model: Electronic Cited Medium: Internet ISSN: 1522-9602 (Electronic) Linking ISSN: 00928240 NLM ISO Abbreviation: Bull Math Biol Subsets: MEDLINE
Imprint Name(s):
Publication: New York, NY : Springer
Original Publication: New York, Pergamon Press.
MeSH Terms:
Protein Biosynthesis*/genetics , Codon Usage*/genetics , Models, Genetic* , RNA, Transfer*/genetics , RNA, Transfer*/metabolism, Mathematical Concepts ; Computer Simulation ; Bacteriophage T7/genetics ; Bacteriophage T7/metabolism ; Codon/genetics ; Stochastic Processes ; Capsid Proteins/genetics ; Capsid Proteins/biosynthesis
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Grant Information:
R01 GM088344 United States GM NIGMS NIH HHS
Contributed Indexing:
Keywords: Codon usage bias; Gene recoding; Translation efficiency; tRNA Dynamics
Substance Nomenclature:
9014-25-9 (RNA, Transfer)
0 (Codon)
0 (Capsid Proteins)
Entry Date(s):
Date Created: 20260113 Date Completed: 20260113 Latest Revision: 20260117
Update Code:
20260117
PubMed Central ID:
PMC12799730
DOI:
10.1007/s11538-025-01587-y
PMID:
41530506
Database:
MEDLINE

Weitere Informationen

Synonymous codon usage can influence protein expression, since codons with high numbers of corresponding tRNAs are naturally translated more rapidly than codons with fewer corresponding tRNAs. Although translation efficiency ultimately depends on the concentration of aminoacylated (charged) tRNAs, many theoretical models of translation have ignored tRNA dynamics and treated charged tRNAs as fixed resources. This simplification potentially limits these models from making accurate predictions in situations where charged tRNAs become limiting. Here, we derive a mathematical model of translation with explicit tRNA dynamics and tRNA re-charging, based on a stochastic simulation of this system that was previously applied to investigate codon usage in the context of gene overexpression. We use the mathematical model to systematically explore the relationship between codon usage and the protein expression rate, and find that in the regime where tRNA charging is a limiting reaction, it is always optimal to match codon frequencies to the tRNA pool. Conversely, when tRNA charging is not limiting, using 100% of the preferred codon is optimal for protein production. We also use the tRNA dynamics model to augment a whole-cell simulation of bacteriophage T7. Using this model, we demonstrate that the high expression rate of the T7 major capsid gene causes rare charged tRNAs to become entirely depleted, which explains the sensitivity of the major capsid gene to codon deoptimization.
(© 2025. The Author(s).)

Declarations. Competing interests: The authors declare no competing interests.