Codon usage is an important determinant of gene expression levels largely through its effects on transcription

Zhipeng Zhoua, Yunkun Danga, Mian Zhou, Lin Li, Chien-hung Yu, Jingjing Fu, She Chen, Yi Liu

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Codon usage biases are found in all eukaryotic and prokaryotic genomes, and preferred codons are more frequently used in highly expressed genes. The effects of codon usage on gene expression were previously thought to be mainly mediated by its impacts on translation. Here, we show that codon usage strongly correlates with both protein and mRNA levels genome-wide in the filamentous fungus Neurospora. Gene codon optimization also results in strong up-regulation of protein and RNA levels, suggesting that codon usage is an important determinant of gene expression. Surprisingly, we found that the impact of codon usage on gene expression results mainly from effects on transcription and is largely independent of mRNA translation and mRNA stability. Furthermore, we show that histone H3 lysine 9 trimethylation is one of the mechanisms responsible for the codon usage-mediated transcriptional silencing of some genes with nonoptimal codons. Together, these results uncovered an unexpected important role of codon usage in ORF sequences in determining transcription levels and suggest that codon biases are an adaptation of protein coding sequences to both transcription and translation machineries. Therefore, synonymous codons not only specify protein sequences and translation dynamics, but also help determine gene expression levels.

Original languageEnglish
Pages (from-to)E6117-E6125
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number41
DOIs
Publication statusPublished - 2016 Oct 11

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Codon
Gene Expression
Protein Biosynthesis
Genome
Neurospora
Proteins
RNA Stability
Gene Silencing
Histones
Open Reading Frames
Genes
Lysine
Fungi
Up-Regulation
RNA
Messenger RNA

All Science Journal Classification (ASJC) codes

  • General

Cite this

Zhoua, Zhipeng ; Danga, Yunkun ; Zhou, Mian ; Li, Lin ; Yu, Chien-hung ; Fu, Jingjing ; Chen, She ; Liu, Yi. / Codon usage is an important determinant of gene expression levels largely through its effects on transcription. In: Proceedings of the National Academy of Sciences of the United States of America. 2016 ; Vol. 113, No. 41. pp. E6117-E6125.
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Codon usage is an important determinant of gene expression levels largely through its effects on transcription. / Zhoua, Zhipeng; Danga, Yunkun; Zhou, Mian; Li, Lin; Yu, Chien-hung; Fu, Jingjing; Chen, She; Liu, Yi.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 113, No. 41, 11.10.2016, p. E6117-E6125.

Research output: Contribution to journalArticle

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