ArticleNature biotechnology2018
Evaluation of 244,000 synthetic sequences reveals design principles to optimize translation in Escherichia coli.
Article in Nature biotechnology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.
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Who cites it
107 citing papers in PubMed, 248 citations in OpenAlex.
- N-terminal fusion length: The key to reliable and context-preserving regulatory sequence characterization.Synthetic and systems biotechnology · 2027Article
- Systematic optimization ofEngineering microbiology · 2026Review
- Approaches for Studying Context Specificity of Translation Inhibitor Action.International journal of molecular sciences · 2026Review
- Developing the protein quality control system inSynthetic and systems biotechnology · 2026Article
- Highly mutagenic continuous evolution in E. coli using a Φ29-based orthogonal replication system.Nature biotechnology · 2026Article
- Hurdles to horizontal gene transfer: species-specific effects of synonymous variation and plasmid copy number determine antibiotic resistance phenotype.Microbiology (Reading, England) · 2026Article
- Article
- Bacterial gene 5' ends have unusual mutation rates that can mislead tests of selection.PLoS biology · 2025Article
- Base composition at the start of the coding sequence controls the balance between translation initiation and mRNA degradation in E. coli.Nucleic acids research · 2025Article
- Dual-channel heterogeneous feature fusion neural network for the prediction of post-transcriptional gene expression in Escherichia coli.BMC bioinformatics · 2025Article
- OPT: Codon optimize gene sequences for E. coli protein overexpression.Journal of molecular biology · 2025Article
- Why AGG is associated with high transgene output: passenger effects and their implications for transgene design.NAR genomics and bioinformatics · 2025Article
- Stress-induced phase separation in plastics drives the release of amorphous polymer micropollutants into water.Nature communications · 2025Article
- Untranslated region engineering strategies for gene overexpression, fine-tuning, and dynamic regulation.Journal of microbiology (Seoul, Korea) · 2025Review
- Increasing recombinant protein production in E. coli via FACS-based selection of N-terminal coding DNA libraries.The FEBS journal · 2025Article
- Role of Ribosomal Protein bS1 in Orthogonal mRNA Start Codon Selection.Biochemistry · 2025Article
- Translation of the downstream ORF from bicistronic mRNAs by human cells: Impact of codon usage and splicing in the upstream ORF.Protein science : a publication of the Protein Society · 2025Article
- Improving the generalization of protein expression models with mechanistic sequence information.Nucleic acids research · 2025Article
- Millennial-scale microbiome analysis reveals ancient antimicrobial resistance conserved despite modern selection pressures.Environmental microbiome · 2024Article
- The expression of integron arrays is shaped by the translation rate of cassettes.Nature communications · 2024Article
47 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Comparative analyses of natural and mutated sequences have been used to probe mechanisms of gene expression, but small sample sizes may produce biased outcomes. We applied an unbiased design-of-experiments approach to disentangle factors suspected to affect translation efficiency in E. coli. We precisely designed 244,000 DNA sequences implementing 56 replicates of a full factorial design to evaluate nucleotide, secondary structure, codon and amino acid properties in combination. For each sequence, we measured reporter transcript abundance and decay, polysome profiles, protein production and growth rates. Associations between designed sequences properties and these consequent phenotypes were dominated by secondary structures and their interactions within transcripts. We confirmed that transcript structure generally limits translation initiation and demonstrated its physiological cost using an epigenetic assay. Codon composition has a sizable impact on translatability, but only in comparatively rare elongation-limited transcripts. We propose a set of design principles to improve translation efficiency that would benefit from more accurate prediction of secondary structures in vivo.
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Registered trials
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.