Evidence map›Paper›PMID 26760206›Full record

ArticleNature2016

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

Grégory Boël, Reka Letso, Helen Neely, W Nicholson Price, Kam-Ho Wong, Min Su, Jon Luff, Mayank Valecha, John K Everett, Thomas B Acton and 4 more

Open access · greenAbstract read
In one paragraph

Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 236 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
236citing papers in PubMed, 2 pooled it
28.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

236 citing papers in PubMed, 2 syntheses or guidelines pooled it, 457 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
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176 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 1 country.

Grégory BoëlDepartment of Biological Sciences, 702A Fairchild Center, MC2434, Columbia University, New York, NY 10027, USA.
Reka Letso *Department of Biological Sciences, 702A Fairchild Center, MC2434, Columbia University, New York, NY 10027, USA.
Helen Neely *Department of Biological Sciences, 702A Fairchild Center, MC2434, Columbia University, New York, NY 10027, USA.
W Nicholson Price *Department of Biological Sciences, 702A Fairchild Center, MC2434, Columbia University, New York, NY 10027, USA.
Kam-Ho WongDepartment of Biological Sciences, 702A Fairchild Center, MC2434, Columbia University, New York, NY 10027, USA.
Min SuDepartment of Biological Sciences, 702A Fairchild Center, MC2434, Columbia University, New York, NY 10027, USA.
Jon LuffDepartment of Biological Sciences, 702A Fairchild Center, MC2434, Columbia University, New York, NY 10027, USA.
Mayank ValechaDepartment of Biological Sciences, 702A Fairchild Center, MC2434, Columbia University, New York, NY 10027, USA.
John K EverettNortheast Structural Genomics Consortium; Institut de Biologie Physico-Chimique, 13-rue Pierre et Marie Curie, 75005 Paris, France.
Thomas B ActonNortheast Structural Genomics Consortium; Institut de Biologie Physico-Chimique, 13-rue Pierre et Marie Curie, 75005 Paris, France.
Rong XiaoNortheast Structural Genomics Consortium; Institut de Biologie Physico-Chimique, 13-rue Pierre et Marie Curie, 75005 Paris, France.
Gaetano T MontelioneNortheast Structural Genomics Consortium; Institut de Biologie Physico-Chimique, 13-rue Pierre et Marie Curie, 75005 Paris, France.
Daniel P AalbertsDepartment of Physics, Williams College, Williamstown, MA 01267, USA.
John F HuntDepartment of Biological Sciences, 702A Fairchild Center, MC2434, Columbia University, New York, NY 10027, USA.
Columbia University · USNew York Structural Biology Center · USRutgers, The State University of New Jersey · USWilliams College · US

Funding

University of Georgia ProjectU54GM094597 · NIGMS · RUTGERS, THE STATE UNIV OF N.J. · PI SZYPERSKI, THOMAS A. · 2010 to 2014
$36.9M
AREA: Optimizing gene expression with mRNA free energy modeling and algorithmsR15GM106372 · NIGMS · WILLIAMS COLLEGE · PI AALBERTS, DANIEL PAUL · 2014 to 2014
$255k
NIGMS NIH HHS GM106372NIGMS NIH HHS R15 GM106372NIGMS NIH HHS U54 GM094597NIGMS NIH HHS U54-GM094597
6 · The paper itself

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.

Indexed as

CodonDNA-Directed RNA PolymerasesEscherichia coliEscherichia coli ProteinsGene Expression Regulation, BacterialGenes, SyntheticHalf-LifeKineticsLogistic ModelsModels, GeneticMolecular Sequence DataOdds RatioPeptide Chain Elongation, TranslationalProtein BiosynthesisRNA, BacterialRNA Foldingbacteriophage T7 RNA polymeraseCodonDNA-Directed RNA PolymerasesEscherichia coli ProteinsRNA, BacterialRNA, MessengerViral Proteins

Identifiers

PMID26760206
PMCPMC5054687
OpenAlexW2259283565

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.