Growth-Optimized Aminoacyl-tRNA Synthetase Levels Prevent Maximal tRNA Charging
Name
nihms-1615897.pdf
Description
Accepted version
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2.09 MB
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Adobe PDF
Checksum (MD5)
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Author(s)
Parker, Darren J.
Lalanne, Jean-Benoit
Kimura, Satoshi
Johnson, Grace E.
Waldor, Matthew K
Li, Gene-Wei
Date Issued
2020
Journal
Cell Systems
Publisher
Elsevier BV
Citation
Parker, Darren J., Lalanne, Jean-Benoit, Kimura, Satoshi, Johnson, Grace E., Waldor, Matthew K et al. 2020. "Growth-Optimized Aminoacyl-tRNA Synthetase Levels Prevent Maximal tRNA Charging." Cell Systems, 11 (2).
Version
Author's final manuscript
Abstract
© 2020 Elsevier Inc. Aminoacyl-tRNA synthetases (aaRSs) serve a dual role in charging tRNAs. Their enzymatic activities both provide protein synthesis flux and reduce uncharged tRNA levels. Although uncharged tRNAs can negatively impact bacterial growth, substantial concentrations of tRNAs remain deacylated even under nutrient-rich conditions. Here, we show that tRNA charging in Bacillus subtilis is not maximized due to optimization of aaRS production during rapid growth, which prioritizes demands in protein synthesis over charging levels. The presence of uncharged tRNAs is alleviated by precisely tuned translation kinetics and the stringent response, both insensitive to aaRS overproduction but sharply responsive to underproduction, allowing for just enough aaRS production atop a “fitness cliff.” Notably, we find that the stringent response mitigates fitness defects at all aaRS underproduction levels even without external starvation. Thus, adherence to minimal, flux-satisfying protein production drives limited tRNA charging and provides a basis for the sensitivity and setpoints of an integrated growth-control network.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Physics
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.CELS.2020.07.005
