Genome-wide role of codon usage on transcription and identification of potential regulators

Fangzhou Zhao, Zhipeng Zhou, Yunkun Dang, Hyunsoo Na, Catherine Adam, Anna Lipzen, Vivian Ng, Igor V. Grigoriev, Yi Liu

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Codon usage bias is a fundamental feature of all genomes and plays an important role in determining gene expression levels. The codon usage was thought to influence gene expression mainly due to its impact on translation. Recently, however, codon usage was shown to affect transcription of fungal and mammalian genes, indicating the existence of a gene regulatory phenomenon with unknown mechanism. In Neurospora, codon usage biases strongly correlate with mRNA levels genome-wide, and here we show that the correlation between codon usage and RNA levels is maintained in the nucleus. In addition, codon optimality is tightly correlated with both total and nuclear RNA levels, suggesting that codon usage broadly influences mRNA levels through transcription in a translation-independent manner. A large-scale RNA sequencing-based genetic screen in Neurospora identified 18 candidate factors that when deleted decreased the genome-wide correlation between codon usage and RNA levels and reduced the codon usage effect on gene expression. Most of these factors, such as the H3K36 methyltransferase, are chromatin regulators or transcription factors. Together, our results suggest that the transcriptional effect of codon usage is mediated by multiple transcriptional regulatory mechanisms.

Original languageEnglish (US)
Article numbere2022590118
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number6
StatePublished - Feb 9 2021
Externally publishedYes


  • Codon usage
  • H3K36 methyltransferase
  • Neurospora
  • Transcription
  • Translation

ASJC Scopus subject areas

  • General


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