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

Elife. 2018 Sep 7:7:e32536. doi: 10.7554/eLife.32536.


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 min - 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.

Keywords: S. cerevisiae; chromosomes; decay; gene expression; genetics; genomics; mRNA; translation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biotin / metabolism
  • Cell Proliferation
  • Computer Simulation
  • Half-Life
  • Kinetics
  • Protein Biosynthesis*
  • RNA Stability / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reproducibility of Results
  • Ribosomes / metabolism
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Staining and Labeling
  • Transcriptome / genetics


  • RNA, Messenger
  • Biotin