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

Chan, L. Y.; Mugler, C. F.; Heinrich, S.; Vallotton, P.; Weis, K.

doi:10.1101/214775

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bioRxiv · 10.1101/214775

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

Chan, L. Y.·Mugler, C. F.·Heinrich, S.·Vallotton, P.·Weis, K.

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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.

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Chan, L. Y., Mugler, C. F., Heinrich, S., Vallotton, P., Weis, K.. 2017-11-07. Non-invasive measurement of mRNA decay reveals translation initiation as the major determinant of mRNA stability. https://doi.org/10.1101/214775

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