Cited by 117RNA and protein synthesis mechanismsRNA Research and SplicingRNA modifications and cancer

Codon and amino acid content are associated with mRNA stability in mammalian cells

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Forrest, Megan E., Pinkard, Otis, Martin, Sophie, Sweet, Thomas J., Hanson, Gavin, Coller, Jeff·2020·PLOS ONE

Abstract

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-life.

    “Prior work has demonstrated strong relationships between codon usage and mRNA half-life23,78.”
  • There is a correlation between codon-aggregated gradient saliencies of gene exon coverage and MPRA measurements from a previous publication (Pearson's R = 0.59).

    “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]

    The Results section describes codon-dependent mRNA stability measured with individual reporter constructs, and the Methods describe their measurement by northern blot. Searches for “MPRA,” “massively parallel,” and “0.59” found no passage identifying MPRA measurements in this paper. The cited paper also cannot verify the citing authors’ correlation with their own gradient saliencies. (LLM, conf=0.75)

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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
Published
2020-02-13
Volume
15
Issue
2
Pages
e0228730
ISSN
1932-6203 (ISSN-L)
OpenAlex
W3006243445
Cited by
116
References
104
Citations by year
2026: 15 · 2025: 23 · 2024: 25 · 2023: 15 · 2022: 12 · 2021: 15 · 2020: 9 · 2019: 1
FWCI
4.14
Type
journal article
Language
en
Open access
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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