Codon Usage Influences the Local Rate of Translation Elongation to Regulate Co-translational Protein Folding

Chien Hung Yu, Yunkun Dang, Zhipeng Zhou, Cheng Wu, Fangzhou Zhao, Matthew S. Sachs, Yi Liu

Research output: Contribution to journalArticlepeer-review

361 Scopus citations


Codon usage bias is a universal feature of eukaryotic and prokaryotic genomes and has been proposed to regulate translation efficiency, accuracy, and protein folding based on the assumption that codon usage affects translation dynamics. The roles of codon usage in translation, however, are not clear and have been challenged by recent ribosome profiling studies. Here we used a Neurospora cell-free translation system to directly monitor the velocity of mRNA translation. We demonstrated that the preferred codons enhance the rate of translation elongation, whereas non-optimal codons slow elongation. Codon usage also controls ribosome traffic on mRNA. These conclusions were supported by ribosome profiling results in vitro and in vivo with template mRNAs designed to increase the signal-to-noise ratio. Finally, we demonstrate that codon usage regulates protein function by affecting co-translational protein folding. These results resolve a long-standing fundamental question and suggest the existence of a codon usage code for protein folding. Yu et al. demonstrate that codon usage impacts local translational dynamics: frequently used codons speed up elongation, while non-preferred codons slow it down. The changes of translation elongation rates on mRNAs are adapted to protein structures to facilitate co-translational folding. The results suggest a codon usage "code" for protein structure.

Original languageEnglish (US)
Pages (from-to)744-754
Number of pages11
JournalMolecular cell
Issue number5
StatePublished - Sep 3 2015

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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