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

Autor: Gaetano T. Montelione, W. Nicholson Price, Mayank Valecha, Reka Letso, Thomas Acton, Kam Ho Wong, Grégory Boël, Helen Neely, Min Su, Daniel P. Aalberts, Jon D. Luff, Rong Xiao, John F. Hunt, John K. Everett
Přispěvatelé: Expression Génétique Microbienne (EGM (UMR_8261 / FRE_3630)), Institut de biologie physico-chimique (IBPC (FR_550)), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Northeast Structural Genomics Consortium, Columbia University [New York], Institut de biologie physico-chimique (IBPC)
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
RNA Folding
[SDV.BIO]Life Sciences [q-bio]/Biotechnology
Transcription
Genetic
RNA Stability
Molecular Sequence Data
Peptide Chain Elongation
Translational
Biology
Article
03 medical and health sciences
Viral Proteins
Transcription (biology)
Protein biosynthesis
Escherichia coli
Genes
Synthetic
Odds Ratio
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
RNA
Messenger
Codon
Gene
ComputingMilieux_MISCELLANEOUS
Regulation of gene expression
Genetics
Messenger RNA
Multidisciplinary
Models
Genetic
Escherichia coli Proteins
RNA
DNA-Directed RNA Polymerases
Gene Expression Regulation
Bacterial
Genetic code
[SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM]
Kinetics
RNA
Bacterial
030104 developmental biology
Logistic Models
Codon usage bias
Protein Biosynthesis
Half-Life
Zdroj: Nature
Nature, Nature Publishing Group, 2016, 529 (7586), pp.358-363. ⟨10.1038/nature16509⟩
ISSN: 0028-0836
1476-4679
DOI: 10.1038/nature16509⟩
Popis: 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.
Databáze: OpenAIRE
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