ArticleNucleic acids research2021
Codon usage and protein length-dependent feedback from translation elongation regulates translation initiation and elongation speed.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 65 citations in OpenAlex.
- Codon Optimality Modulates Cellular Stress and Innate Immune Responses Triggered by Exogenous RNAs.Journal of molecular biology · 2026Article
- STRIPAK-associated greenbeard proteins DOC1 and DOC2 regulate MAK2 signaling and sexual development in Sordaria macrospora.PLoS biology · 2026Article
- APOE4 disrupts the central dogma by arresting neuronal proteome dynamics.bioRxiv : the preprint server for biology · 2026Article
- Coordinated translation initiation determines -1 programmed ribosomal frameshifting efficiency of chromosomal genes to impact on cell fitness.The FEBS journal · 2026Article
- AI-guided redesign of laboratory-evolved reverse transcriptases enhances prime editing.Nature biotechnology · 2026Article
- Immune cell annotation in the single-cell studies: technologies, challenges, and integrative solutions.Immunologic research · 2026Review
- In vivo CAR-T therapy: from molecular design to precision delivery.Journal of nanobiotechnology · 2026Review
- Evolution and Functional Implications of Codon Usage Bias in Eukaryotes.Journal of molecular evolution · 2026Review
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- Effects of Korean red ginseng on the HIV-1Journal of ginseng research · 2026Article
- Nuclear effects play an important role in determining codon usage-dependent human gene expression.Nature communications · 2025Article
- The intrinsic properties of mRNAs define their translation efficiency at ribosome shortage.Nucleic acids research · 2025Article
- Primary Sequence-Intrinsic Immune Evasion by Viral Proteins Guides CTL-Based Vaccine Strategies.Viruses · 2025Review
- Respiratory syncytial virus (RSV) enhances translation of virus-resembling AU-rich host transcripts.Virology journal · 2025Article
- Emerging mechanisms of human mitochondrial translation regulation.Trends in biochemical sciences · 2025Review
- Natural Selection as the Primary Driver of Codon Usage Bias in the Mitochondrial Genomes of ThreeGenes · 2025Article
- Dysregulated ribosome quality control in human diseases.The FEBS journal · 2025Review
- 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 polyketide biosynthesis by rescuing the translation of truncated mRNAs into functional polyketide synthase subunits.Nature communications · 2025Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Essential cellular functions require efficient production of many large proteins but synthesis of large proteins encounters many obstacles in cells. Translational control is mostly known to be regulated at the initiation step. Whether translation elongation process can feedback to regulate initiation efficiency is unclear. Codon usage bias, a universal feature of all genomes, plays an important role in determining gene expression levels. Here, we discovered that there is a conserved but codon usage-dependent genome-wide negative correlation between protein abundance and CDS length. The codon usage effects on protein expression and ribosome flux on mRNAs are influenced by CDS length; optimal codon usage preferentially promotes production of large proteins. Translation of mRNAs with long CDS and non-optimal codon usage preferentially induces phosphorylation of initiation factor eIF2α, which inhibits translation initiation efficiency. Deletion of the eIF2α kinase CPC-3 (GCN2 homolog) in Neurospora preferentially up-regulates large proteins encoded by non-optimal codons. Surprisingly, CPC-3 also inhibits translation elongation rate in a codon usage and CDS length-dependent manner, resulting in slow elongation rates for long CDS mRNAs. Together, these results revealed a codon usage and CDS length-dependent feedback mechanism from translation elongation to regulate both translation initiation and elongation kinetics.
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