ArticleCell2015
Codon optimality is a major determinant of mRNA stability.
Article in Cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 652 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
652 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Fitness costs of mobilised colistin resistance gene 3 (mcr-3): systematic review, epidemiological study, and functional analysis.EBioMedicine · 2025Pooled it
- Codon-dependent translation of N1-ethylpseudouridine-modified mRNA reduces innate immunity while preserving vaccine immunogenicity.Molecular therapy. Nucleic acids · 2026Article
- 5PSeq Explorer: interactive analysis of co-translational mRNA decay and ribosome dynamics.RNA biology · 2026Article
- Codon Optimality Modulates Cellular Stress and Innate Immune Responses Triggered by Exogenous RNAs.Journal of molecular biology · 2026Article
- Global Regulatory Functions of the Human CCR4-NOT Complex in mRNA Deadenylation and Decay.bioRxiv : the preprint server for biology · 2026Article
- Towards mRNA therapeutics 2.0.Nature reviews. Drug discovery · 2026Review
- Circular Photocaged mRNA for Light-induced Late-stage Activation of Translation.Angewandte Chemie (International ed. in English) · 2026Article
- Codon optimality predicts mRNA half-life but does not transfer to lncRNAs.Molecular genetics and genomics : MGG · 2026Article
- Beyond codon optimality: codon pairs regulate mRNA stability dependent on translation.bioRxiv : the preprint server for biology · 2026Article
- Review
- Enhancing protein expression in humans through codon optimization with transformer and contrastive learning.Molecular therapy. Nucleic acids · 2026Article
- Codon-optimizedMolecular therapy. Nucleic acids · 2026Article
- Transgene sequence codon optimization and composition determines replication competence of self-amplifying RNA.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Principles of ribosome-associated protein quality control during the synthesis of CFTR.The EMBO journal · 2026Article
- USP15 mutation associated with autism spectrum disorder alters progenitor fate and neuronal maturation in human brain organoids.Molecules and cells · 2026Article
- Spatial mapping of RNA turnover kinetics in the mouse brain.Nature neuroscience · 2026Article
- Gradient-based optimization for mRNA sequence design.Bioinformatics (Oxford, England) · 2026Article
- The Tor pathway, ribosome concentration, and wobble decoding mediate inhibitory effects of the Leu-Pro CUC-CCG codon pair inRNA (New York, N.Y.) · 2026Article
- Heat stress promotes pre-tRNA capping to modulate cap-dependent translation in Saccharomyces cerevisiae.Nature communications · 2026Article
- Nascent chain folding status modulates ribosome dynamics and mRNA stability through the ribosome-associated chaperone Zuo1.Molecular cell · 2026Article
592 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
mRNA degradation represents a critical regulated step in gene expression. Although the major pathways in turnover have been identified, accounting for disparate half-lives has been elusive. We show that codon optimality is one feature that contributes greatly to mRNA stability. Genome-wide RNA decay analysis revealed that stable mRNAs are enriched in codons designated optimal, whereas unstable mRNAs contain predominately non-optimal codons. Substitution of optimal codons with synonymous, non-optimal codons results in dramatic mRNA destabilization, whereas the converse substitution significantly increases stability. Further, we demonstrate that codon optimality impacts ribosome translocation, connecting the processes of translation elongation and decay through codon optimality. Finally, we show that optimal codon content accounts for the similar stabilities observed in mRNAs encoding proteins with coordinated physiological function. This work demonstrates that codon optimization exists as a mechanism to finely tune levels of mRNAs and, ultimately, proteins.
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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.