Evidence map›Paper›PMID 32726597›Full record

ArticleCell systems2020

Growth-Optimized Aminoacyl-tRNA Synthetase Levels Prevent Maximal tRNA Charging.

Darren J Parker, Jean-Benoît Lalanne, Satoshi Kimura, Grace E Johnson, Matthew K Waldor, Gene-Wei Li

Open access · bronzeAbstract read
In one paragraph

Article in Cell systems, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.5field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 46 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Darren J ParkerDepartment of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Jean-Benoît LalanneDepartment of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Satoshi KimuraDivision of Infectious Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
Grace E JohnsonDepartment of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Matthew K WaldorDivision of Infectious Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
Gene-Wei LiDepartment of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: gwli@mit.edu.
Massachusetts Institute of Technology · USBrigham and Women's Hospital · US

Funding

PRE-DOCTORAL TRAINING IN THE BIOLOGICAL SCIENCEST32GM007287 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BELL, STEPHEN P., KEATING, AMY E · 1985 to 2019
$40.8M
Vibrio cholerae intestinal colonization and vaccine developmentR01AI042347 · NIAID · TUFTS UNIVERSITY BOSTON · PI WALDOR, MATTHEW K · 1998 to 2025
$7.3M
Evolution and Regulation of Bacterial Proteome CompositionR35GM124732 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Gene-Wei Li · 2017 to 2026
$3.8M
Howard Hughes Medical InstituteNIAID NIH HHS R01 AI042347NIGMS NIH HHS R35 GM124732NIGMS NIH HHS T32 GM007287
6 · The paper itself

Abstract

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.

Indexed as

Amino Acyl-tRNA SynthetasesHumansRNA, TransferAmino Acyl-tRNA SynthetasesRNA, Transferaminoacylationaminoacyl-tRNA synthetasebacteriagene expressiongrowth controlgrowth optimizationtranslationuncharged tRNA

Identifiers

PMID32726597
PMCPMC7484455
OpenAlexW3046093905

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.