Translation affects mRNA stability in a codon-dependent manner in human cells
Open accessAbstract
mRNA translation decodes nucleotide into amino acid sequences. However, translation has also been shown to affect mRNA stability depending on codon composition in model organisms, although universality of this mechanism remains unclear. Here, using three independent approaches to measure exogenous and endogenous mRNA decay, we define which codons are associated with stable or unstable mRNAs in human cells. We demonstrate that the regulatory information affecting mRNA stability is encoded in codons and not in nucleotides. Stabilizing codons tend to be associated with higher tRNA levels and higher charged/total tRNA ratios. While mRNAs enriched in destabilizing codons tend to possess shorter poly(A)-tails, the poly(A)-tail is not required for the codon-mediated mRNA stability. This mechanism depends on translation; however, the number of ribosome loads into a mRNA modulates the codon-mediated effects on gene expression. This work provides definitive evidence that translation strongly affects mRNA stability in a codon-dependent manner in human cells.
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Codon preference varies extensively in different organisms; adjusting the balance between codon usage frequency and host tRNA availability can significantly improve translation efficiency and in vivo expression of the target antigen.
“Codon preference varies extensively in different organisms,249 therefore adjusting the balance between codon usage frequency and host tRNA availability can significantly improve translation efficiency and in vivo expression of the target antigen.250,251”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [250]
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References 66 · Cited by 283
- Authors
- Wu, Q., Medina, S. G., Kushawah, G., DeVore, M. L., Castellano, L. A., Hand, J. M., Wright, M., & Bazzini, A. A.
- Affiliations
- Stowers Institute for Medical Research (US)
- Stowers Institute for Medical Research, Kansas City, United States
- Corresponding author
- Bazzini, Ariel Alejandro
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2019-04-23
- Volume
- 8
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC6529216
- OpenAlex
- W2940525406
- Cited by
- 283
- References
- 66
- Citations by year
- 2026: 29 · 2025: 45 · 2024: 57 · 2023: 38 · 2022: 36 · 2021: 42 · 2020: 30 · 2019: 6
- FWCI
- 9.43
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Stowers Institute for Medical Research
- 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, codon composition, translation (biology), poly(A) tail, gene expression regulation, human cells
- MeSH terms
- Cell Line, Codon, Humans, Protein Biosynthesis, RNA Stability
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