Cited by 254RNA and protein synthesis mechanismsProtein Structure and DynamicsRNA Research and Splicing

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A code within the genetic code: codon usage regulates co-translational protein folding

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Liu, Yi·2020·Cell Communication and Signaling

DOI 10.1186/s12964-020-00642-6PMC PMC7488015

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Abstract

The genetic code is degenerate, and most amino acids are encoded by two to six synonymous codons. Codon usage bias, the preference for certain synonymous codons, is a universal feature of all genomes examined. Synonymous codon mutations were previously thought to be silent; however, a growing body evidence now shows that codon usage regulates protein structure and gene expression through effects on co-translational protein folding, translation efficiency and accuracy, mRNA stability, and transcription. Codon usage regulates the speed of translation elongation, resulting in non-uniform ribosome decoding rates on mRNAs during translation that is adapted to co-translational protein folding process. Biochemical and genetic evidence demonstrate that codon usage plays an important role in regulating protein folding and function in both prokaryotic and eukaryotic organisms. Certain protein structural types are more sensitive than others to the effects of codon usage on protein folding, and predicted intrinsically disordered domains are more prone to misfolding caused by codon usage changes than other domain types. Bioinformatic analyses revealed that gene codon usage correlates with different protein structures in diverse organisms, indicating the existence of a codon usage code for co-translational protein folding. This review focuses on recent literature on the role and mechanism of codon usage in regulating translation kinetics and co-translational protein folding. Video abstract.

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Fig. 1 a The known translation-dependent roles of codon usage. b A model depicting the role of codon usage in regulating translation elongation speed and co-translational protein folding. c A model depicting that when codon usage is not optimally adapted to the co-translational protein folding process, protein misfolding increasesCC BY · PubMed Central

Fig. 2 Protein disorder tendency plots of the Neurospora FRQ, Drosophila PER, and Synechococcus KaiC proteins. Protein disorder tendency is predicted by the IUPred2A web interface (https://iupred2a.elte.hu/)CC BY · PubMed Central

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Authors: Liu, Y.
Affiliations: The University of Texas Southwestern Medical Center (US)
Corresponding author: Liu, Yi
ORCID: Liu, Yi
Venue: Cell Communication and Signaling
Publisher: Springer Science and Business Media LLC
Published: 2020-09-09
Volume: 18
Issue: 1
Pages: 145-145
ISSN: 1478-811X (ISSN-L)
DOI: 10.1186/s12964-020-00642-6
PMC: PMC7488015
OpenAlex: W3083874241
Cited by: 252
References: 105
Citations by year: 2026: 29 · 2025: 54 · 2024: 63 · 2023: 48 · 2022: 36 · 2021: 21 · 2020: 1
FWCI: 2.54
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0 (tdm)
creativecommons.org/licenses/by/4.0 (vor)
Locations: Cell Communication and Signaling (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Institute of General Medical Sciences (R35GM118118)
Welch Foundation (I-1560)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Keywords: codon usage bias, co-translational folding, synonymous codons, genetic code degeneracy, translation elongation rate, intrinsically disordered regions, protein misfolding, translation efficiency, mRNA stability
MeSH terms: Codon Usage, Animals, Genetic Code, Humans, Protein Conformation, Proteins, RNA, Messenger, Protein Biosynthesis, Protein Folding, Intrinsically Disordered Proteins

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A code within the genetic code: codon usage regulates co-translational protein folding

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