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

Abstract
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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

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(2018) mRNA stability as measured by thiouracil incorporation in the presence and absence of translational inhibitors
ublicly available at the NCBI Gene Expression Omnibus (accession no: GSE119560).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE119560

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Article and author information

Author details

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.

"This ORCID iD identifies the author of this article:" 0000-0002-0189-4689
Christopher F Mugler

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0001-8258-1192
Stephanie Heinrich

Department of Biochemistry, ETH Zurich, Zurich, Switzerland

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0003-1607-4525
Pascal Vallotton

Department of Biochemistry, ETH Zurich, Zurich, Switzerland

Competing interests
No competing interests declared.
Karsten Weis

Department of Biochemistry, ETH Zurich, Zurich, Switzerland

For correspondence
karsten.weis@bc.biol.ethz.ch

Competing interests
Karsten Weis, Reviewing editor, eLife.

"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.

Copyright

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.