ArticleJournal of molecular biology2010
Multifactorial determinants of protein expression in prokaryotic open reading frames.
Article in Journal of molecular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 105 citations in OpenAlex.
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- Mutational biases and selection in mitochondrial genomes: insights from a comparative analysis of natural and laboratory populations of Caenorhabditis elegans.G3 (Bethesda, Md.) · 2026Article
- Bacterial gene 5' ends have unusual mutation rates that can mislead tests of selection.PLoS biology · 2025Article
- Combinatorial mutagenesis of N-terminal sequences reveals unexpected and expanded stability determinants of thebioRxiv : the preprint server for biology · 2025Article
- Why AGG is associated with high transgene output: passenger effects and their implications for transgene design.NAR genomics and bioinformatics · 2025Article
- Increasing recombinant protein production in E. coli via FACS-based selection of N-terminal coding DNA libraries.The FEBS journal · 2025Article
- The expression of integron arrays is shaped by the translation rate of cassettes.Nature communications · 2024Article
- Selection on synonymous sites: the unwanted transcript hypothesis.Nature reviews. Genetics · 2024Review
- Genes for highly abundant proteins in Escherichia coli avoid 5' codons that promote ribosomal initiation.PLoS computational biology · 2023Article
- Large-scale analysis of mRNA sequences localized near the start and amber codons and their impact on the diversity of mRNA display libraries.Nucleic acids research · 2023Article
- Unexpected myriad of co-occurring viral strains and species in one of the most abundant and microdiverse viruses on Earth.The ISME journal · 2022Article
- Nascent polypeptide within the exit tunnel stabilizes the ribosome to counteract risky translation.The EMBO journal · 2021Article
- A 68-codon genetic code to incorporate four distinct non-canonical amino acids enabled by automated orthogonal mRNA design.Nature chemistry · 2021Article
- Importance of the 5' regulatory region to bacterial synthetic biology applications.Microbial biotechnology · 2021Review
- Inferring Adaptive Codon Preference to Understand Sources of Selection Shaping Codon Usage Bias.Molecular biology and evolution · 2021Article
- Improving the Expression of Human Granulocyte Colony Stimulating Factor in Escherichia coli by Reducing the GC-content and Increasing mRNA Folding Free Energy at 5'-Terminal End.Advanced pharmaceutical bulletin · 2020Article
- Determinants of translation efficiency in the evolutionarily-divergent protist Trichomonas vaginalis.BMC molecular and cell biology · 2020Article
- Translation at first sight: the influence of leading codons.Nucleic acids research · 2020Article
- Translational Control by Ribosome Pausing in Bacteria: How a Non-uniform Pace of Translation Affects Protein Production and Folding.Frontiers in microbiology · 2020Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
A quantitative description of the relationship between protein expression levels and open reading frame (ORF) nucleotide sequences is important for understanding natural systems, designing synthetic systems, and optimizing heterologous expression. Codon identity, mRNA secondary structure, and nucleotide composition within ORFs markedly influence expression levels. Bioinformatic analysis of ORF sequences in 816 bacterial genomes revealed that these features show distinct regional trends. To investigate their effects on protein expression, we designed 285 synthetic genes and determined corresponding expression levels in vitro using Escherichia coli extracts. We developed a mathematical function, parameterized using this synthetic gene data set, which enables computation of protein expression levels from ORF nucleotide sequences. In addition to its practical application in the design of heterologous expression systems, this equation provides mechanistic insight into the factors that control translation efficiency. We found that expression is strongly dependent on the presence of high AU content and low secondary structure in the ORF 5' region. Choice of high-frequency codons contributes to a lesser extent. The 3' terminal AU content makes modest, but detectable contributions. We present a model for the effect of these factors on the three phases of ribosomal function: initiation, elongation, and termination.
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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.