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 journalArticle

154 Citations (Scopus)

Abstract

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
Pages (from-to)744-754
Number of pages11
JournalMolecular Cell
Volume59
Issue number5
DOIs
Publication statusPublished - 2015 Sep 3

Fingerprint

Protein Folding
Codon
Ribosomes
Messenger RNA
Neurospora
Proteins
Cell-Free System
Protein Biosynthesis
Signal-To-Noise Ratio
Genome

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Yu, Chien-hung ; Dang, Yunkun ; Zhou, Zhipeng ; Wu, Cheng ; Zhao, Fangzhou ; Sachs, Matthew S. ; Liu, Yi. / Codon Usage Influences the Local Rate of Translation Elongation to Regulate Co-translational Protein Folding. In: Molecular Cell. 2015 ; Vol. 59, No. 5. pp. 744-754.
@article{f9a180b62fea4d09a38a9fe3bfd3b193,
title = "Codon Usage Influences the Local Rate of Translation Elongation to Regulate Co-translational Protein Folding",
abstract = "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.",
author = "Chien-hung Yu and Yunkun Dang and Zhipeng Zhou and Cheng Wu and Fangzhou Zhao and Sachs, {Matthew S.} and Yi Liu",
year = "2015",
month = "9",
day = "3",
doi = "10.1016/j.molcel.2015.07.018",
language = "English",
volume = "59",
pages = "744--754",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "5",

}

Codon Usage Influences the Local Rate of Translation Elongation to Regulate Co-translational Protein Folding. / Yu, Chien-hung; Dang, Yunkun; Zhou, Zhipeng; Wu, Cheng; Zhao, Fangzhou; Sachs, Matthew S.; Liu, Yi.

In: Molecular Cell, Vol. 59, No. 5, 03.09.2015, p. 744-754.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Codon Usage Influences the Local Rate of Translation Elongation to Regulate Co-translational Protein Folding

AU - Yu, Chien-hung

AU - Dang, Yunkun

AU - Zhou, Zhipeng

AU - Wu, Cheng

AU - Zhao, Fangzhou

AU - Sachs, Matthew S.

AU - Liu, Yi

PY - 2015/9/3

Y1 - 2015/9/3

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84940891331&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84940891331&partnerID=8YFLogxK

U2 - 10.1016/j.molcel.2015.07.018

DO - 10.1016/j.molcel.2015.07.018

M3 - Article

C2 - 26321254

AN - SCOPUS:84940891331

VL - 59

SP - 744

EP - 754

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 5

ER -