Non-invasive measurement of mRNA decay reveals translation initiation as the major determinant of mRNA stability

  1. Leon Y Chan  Is a corresponding author
  2. Christopher F Mugler
  3. Stephanie Heinrich
  4. Pascal Vallotton
  5. Karsten Weis  Is a corresponding author
  1. University of California, Berkeley, United States
  2. ETH Zurich, Switzerland

Abstract

The cytoplasmic abundance of mRNAs is strictly controlled through a balance of production and degradation. Whereas the control of mRNA synthesis through transcription has been well characterized, less is known about the regulation of mRNA turnover, and a consensus model explaining the wide variations in mRNA decay rates remains elusive. Here, we combine non-invasive transcriptome-wide mRNA production and stability measurements with selective and acute perturbations to demonstrate that mRNA degradation is tightly coupled to the regulation of translation, and that a competition between translation initiation and mRNA decay -but not codon optimality or elongation- is the major determinant of mRNA stability in yeast. Our refined measurements also reveal a remarkably dynamic transcriptome with an average mRNA half-life of only 4.8 minutes - much shorter than previously thought. Furthermore, global mRNA destabilization by inhibition of translation initiation induces a dose-dependent formation of processing bodies in which mRNAs can decay over time.

Data availability

Sequencing data have been deposited in GEO under accession code GSE119560.

The following data sets were generated
The following previously published data sets were used
    1. Drummond DA
    2. Raval A
    3. Wilke CO
    (2006) CAI
    Supplementary data: len-cai-fop.txt.

Article and author information

Author details

  1. Leon Y Chan

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    For correspondence
    leonyenleechan@gmail.com
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0189-4689
  2. Christopher F Mugler

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8258-1192
  3. Stephanie Heinrich

    Department of Biochemistry, ETH Zurich, Zurich, Switzerland
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1607-4525
  4. Pascal Vallotton

    Department of Biochemistry, ETH Zurich, Zurich, Switzerland
    Competing interests
    No competing interests declared.
  5. Karsten Weis

    Department of Biochemistry, ETH Zurich, Zurich, Switzerland
    For correspondence
    karsten.weis@bc.biol.ethz.ch
    Competing interests
    Karsten Weis, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7224-925X

Funding

National Institutes of Health

  • Leon Y Chan
  • Christopher F Mugler
  • Karsten Weis

Damon Runyon Cancer Research Foundation

  • Leon Y Chan

Shurl and Kay Curci Foundation

  • Leon Y Chan

European Molecular Biology Organization

  • Stephanie Heinrich

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

  • Stephanie Heinrich
  • Pascal Vallotton
  • Karsten Weis

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

Reviewing Editor

  1. Alan G Hinnebusch, National Institutes of Health, United States

Version history

  1. Received: October 6, 2017
  2. Accepted: August 13, 2018
  3. Accepted Manuscript published: September 7, 2018 (version 1)
  4. Version of Record published: September 24, 2018 (version 2)
  5. Version of Record updated: October 3, 2018 (version 3)
  6. Version of Record updated: February 1, 2019 (version 4)

Copyright

© 2018, Chan 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.

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  1. Leon Y Chan
  2. Christopher F Mugler
  3. Stephanie Heinrich
  4. Pascal Vallotton
  5. Karsten Weis
(2018)
Non-invasive measurement of mRNA decay reveals translation initiation as the major determinant of mRNA stability
eLife 7:e32536.
https://doi.org/10.7554/eLife.32536

Share this article

https://doi.org/10.7554/eLife.32536

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