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Updated: Nov 21, 2025

De novo Identification of Actively Translated Open Reading Frames with Ribosome Profiling Data
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Synonymous but Not Silent: The Codon Usage Code for Gene Expression and Protein Folding.

Yi Liu1, Qian Yang1, Fangzhou Zhao1

  • 1Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9040, USA;

Annual Review of Biochemistry
|January 14, 2021
PubMed
Summary
This summary is machine-generated.

Codon usage bias, the preference for specific synonymous codons, significantly impacts gene expression, protein structure, and mRNA levels. This bias influences translation speed, accuracy, and cotranslational protein folding, revealing its critical regulatory roles.

Keywords:
chromatin structurecodon usagecotranslational protein foldingmRNA decaytranscriptiontranslation efficiencytranslation elongation

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Area of Science:

  • Molecular Biology
  • Genomics
  • Bioinformatics

Background:

  • Codon usage bias, the non-uniform use of synonymous codons, is a pervasive feature across all known genomes.
  • Historically considered 'silent,' synonymous codon variations are now recognized to profoundly influence fundamental biological processes.

Purpose of the Study:

  • To elucidate the multifaceted roles and underlying mechanisms of codon usage bias in gene regulation.
  • To highlight the impact of codon usage on gene expression levels, protein structure, and mRNA stability.

Main Methods:

  • Review and synthesis of existing literature on codon usage bias and its effects.
  • Analysis of genome-wide correlations between codon usage patterns and protein structures.
  • Examination of translation-dependent and independent mechanisms influencing gene regulation.

Main Results:

  • Codon usage bias significantly affects translation elongation speed, efficiency, and accuracy.
  • Bias influences cotranslational protein folding, critical for protein function, and correlates with protein structures.
  • Codon usage impacts mRNA levels through effects on mRNA decay, transcription, and post-transcriptional modifications.

Conclusions:

  • Codon usage bias is a key regulatory mechanism with far-reaching consequences for cellular processes.
  • The adaptation of codon usage to tRNA availability shapes the proteome landscape and gene expression.
  • Understanding codon usage bias is crucial for comprehending gene regulation, protein biogenesis, and genome evolution.