1. Chromosomes and Gene Expression
  2. Genetics and Genomics
Download icon

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
Research Article
  • Cited 0
  • Views 1,013
  • Annotations
Cite as: eLife 2018;7:e32536 doi: 10.7554/eLife.32536

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.

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 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 0000-0001-8258-1192
  3. Stephanie Heinrich

    Department of Biochemistry, ETH Zurich, Zurich, Switzerland
    Competing interests
    No competing interests declared.
    ORCID icon 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 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

Publication history

  1. Received: October 6, 2017
  2. Accepted: August 13, 2018
  3. Accepted Manuscript published: September 7, 2018 (version 1)

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.

Metrics

  • 1,013
    Page views
  • 270
    Downloads
  • 0
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

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)

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

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

Further reading

    1. Chromosomes and Gene Expression
    Julien Bischerour et al.
    Research Article
    1. Chromosomes and Gene Expression
    2. Evolutionary Biology
    Trevor R Sorrells et al.
    Research Article