The DOI matches its Crossref record; 103 of the 104 references it cites were found in a registry or an index.
Codon and amino acid content are associated with mRNA stability in mammalian cells
Open accessAbstract
Messenger RNA (mRNA) degradation plays a critical role in regulating transcript levels in the cell and is a major control point for modulating gene expression. In yeast and other model organisms, codon identity is a powerful determinant of transcript stability, contributing broadly to impact half-lives. General principles governing mRNA stability are poorly understood in mammalian systems. Importantly, however, the degradation machinery is highly conserved, thus it seems logical that mammalian transcript half-lives would also be strongly influenced by coding determinants. Herein we characterize the contribution of coding sequence towards mRNA decay in human and Chinese Hamster Ovary cells. In agreement with previous studies, we observed that synonymous codon usage impacts mRNA stability in mammalian cells. Surprisingly, however, we also observe that the amino acid content of a gene is an additional determinant correlating with transcript stability. The impact of codon and amino acid identity on mRNA decay appears to be associated with underlying tRNA and intracellular amino acid concentrations. Accordingly, genes of similar physiological function appear to coordinate their mRNA stabilities in part through codon and amino acid content. Together, these results raise the possibility that intracellular tRNA and amino acid levels interplay to mediate coupling between translational elongation and mRNA degradation rate in mammals.
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“Prior work has demonstrated strong relationships between codon usage and mRNA half-life23,78.”
From Predicting RNA-seq coverage from DNA sequence as a unifying model of gene regulation (2025) · cites this paper as [78]
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“Although we generally do not find determinants of mRNA half-life in the 3′ UTR attributions, we do observe a correlation between codon-aggregated gradient saliencies of gene exon coverage and MPRA measurements from a previous publication78 (Pearson’ R = 0.59) (Supplementary Fig. 11a).”
From Predicting RNA-seq coverage from DNA sequence as a unifying model of gene regulation (2025) · cites this paper as [78]
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Beyond codon optimality: codon pairs regulate mRNA stability dependent on translationPreprint
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Metadata
- Authors
- Forrest, M. E., Pinkard, O., Martin, S., Sweet, T. J., Hanson, G., & Coller, J.
- Affiliations
- Case Western Reserve University (US)
- Corresponding author
- Coller, Jeff
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2020-02-13
- Volume
- 15
- Issue
- 2
- Pages
- e0228730
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC7018022
- OpenAlex
- W3006243445
- Cited by
- 116
- References
- 104
- Citations by year
- 2026: 15 · 2025: 23 · 2024: 25 · 2023: 15 · 2022: 12 · 2021: 15 · 2020: 9
- FWCI
- 4.14
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- National Institutes of Health (GM125086)
- National Institute of General Medical Sciences (GM118018, T32GM136570)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Keywords
- mRNA stability, mRNA degradation, codon usage, synonymous codons, amino acid content, transcript half-life, translation elongation, gene expression regulation, mammalian cells, CHO cells
- MeSH terms
- Amino Acids, Animals, Codon, Cricetulus, Half-Life, Cricetinae, HeLa Cells, Humans, RNA, Messenger, RNA, Transfer, Open Reading Frames, CHO Cells, RNA Stability
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