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Cited by 440

The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.

Codon influence on protein expression in E. coli correlates with mRNA levels

Open access
Boël, Grégory, Letso, Reka, Neely, Helen, Price, W. Nicholson, Wong, Kam-Ho, Su, Min, Luff, Jon D., Valecha, Mayank, Everett, John K., Acton, Thomas B., Xiao, Rong, Montelione, Gaetano T., Aalberts, Daniel P., Hunt, John F.·2016·Nature

Abstract

Degeneracy in the genetic code, which enables a single protein to be encoded by a multitude of synonymous gene sequences, has an important role in regulating protein expression, but substantial uncertainty exists concerning the details of this phenomenon. Here we analyse the sequence features influencing protein expression levels in 6,348 experiments using bacteriophage T7 polymerase to synthesize messenger RNA in Escherichia coli. Logistic regression yields a new codon-influence metric that correlates only weakly with genomic codon-usage frequency, but strongly with global physiological protein concentrations and also mRNA concentrations and lifetimes in vivo. Overall, the codon content influences protein expression more strongly than mRNA-folding parameters, although the latter dominate in the initial ~16 codons. Genes redesigned based on our analyses are transcribed with unaltered efficiency but translated with higher efficiency in vitro. The less efficiently translated native sequences show greatly reduced mRNA levels in vivo. Our results suggest that codon content modulates a kinetic competition between protein elongation and mRNA degradation that is a central feature of the physiology and also possibly the regulation of translation in E. coli.

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Metadata

Authors
Boël, G., Letso, R., Neely, H., Price, W. N., Wong, K.-H., Su, M., Luff, J. D., Valecha, M., Everett, J. K., Acton, T. B., Xiao, R., Montelione, G. T., Aalberts, D. P., & Hunt, J. F.
Venue
Nature
Published
2016-01-13
Volume
529
Issue
7586
Pages
358-363
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2259283565
Cited by
440
References
59
FWCI
23.02
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Codon influence on protein expression in E. coli correlates with mRNA levels. https://app.cochat.ai/papers/10.1038/nature16509
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Boël, G., Letso, R., Neely, H., Price, W. N., Wong, K.-H., Su, M., Luff, J. D., Valecha, M., Everett, J. K., Acton, T. B., Xiao, R., Montelione, G. T., Aalberts, D. P., & Hunt, J. F. (2016). Codon influence on protein expression in E. coli correlates with mRNA levels. Nature. https://doi.org/10.1038/nature16509

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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