Codon usage biases co-evolve with transcription termination machinery to suppress premature cleavage and polyadenylation

  1. Zhipeng Zhou
  2. Yunkun Dang  Is a corresponding author
  3. Mian Zhou
  4. Haiyan Yuan
  5. Yi Liu  Is a corresponding author
  1. The University of Texas Southwestern Medical Center, United States
  2. Yunnan University, China
  3. East China University of Science and Technology, China

Abstract

Codon usage biases are found in all genomes and influence protein expression levels. The codon usage effect on protein expression was thought to be mainly due to its impact on translation. Here we show that transcription termination is an important driving force for codon usage bias in eukaryotes. Using Neurospora crassa as a model organism, we demonstrated that introduction of rare codons results in premature transcription termination (PTT) within open reading frames and the abolishment of full-length mRNA. PTT is a wide-spread phenomenon in Neurospora and there is a strong negative correlation between codon usage bias and PTT events. Rare codons lead to the formation of putative poly(A) signals and PTT. A similar role for codon usage bias was also observed in mouse. Together, these results suggest that codon usage biases co-evolve with the transcription termination machinery to suppress premature termination of transcription and thus allow for optimal gene expression.

Data availability

The following data sets were generated

Article and author information

Author details

  1. Zhipeng Zhou

    Department of Physiology, The University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Yunkun Dang

    State Key Laboratory of Natural Resource Conservation and Utilization in Yunnan, Yunnan University, Kunming, China
    For correspondence
    yunkun_dang@126.com
    Competing interests
    The authors declare that no competing interests exist.
  3. Mian Zhou

    State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Haiyan Yuan

    Department of Physiology, The University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Yi Liu

    Department of Physiology, The University of Texas Southwestern Medical Center, Dallas, United States
    For correspondence
    yi.liu@utsouthwestern.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8801-9317

Funding

National Institute of General Medical Sciences (R35GM118118)

  • Yi Liu

Cancer Prevention and Research Institute of Texas (RP160268)

  • Yi Liu

Welch Foundation (I-1560)

  • Yi Liu

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2018, Zhou et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 4,112
    views
  • 637
    downloads
  • 72
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Zhipeng Zhou
  2. Yunkun Dang
  3. Mian Zhou
  4. Haiyan Yuan
  5. Yi Liu
(2018)
Codon usage biases co-evolve with transcription termination machinery to suppress premature cleavage and polyadenylation
eLife 7:e33569.
https://doi.org/10.7554/eLife.33569

Share this article

https://doi.org/10.7554/eLife.33569