PT  - JOURNAL ARTICLE
AU  - Leon Y Chan
AU  - Christopher F Mugler
AU  - Stephanie Heinrich
AU  - Pascal Vallotton
AU  - Karsten Weis
TI  - Non-invasive measurement of mRNA decay reveals translation initiation as the major determinant of mRNA stability
AID  - 10.1101/214775
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 214775
4099  - http://biorxiv.org/content/early/2017/11/07/214775.short
4100  - http://biorxiv.org/content/early/2017/11/07/214775.full
AB  - 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.