Evidence map›Paper›PMID 37742077›Full record

ArticleNucleic acids research2023

Coordination between aminoacylation and editing to protect against proteotoxicity.

Hong Zhang, Parker Murphy, Jason Yu, Sukyeong Lee, Francis T F Tsai, Ambro van Hoof, Jiqiang Ling

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.2field-weighted citation impact, top 20% 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

4 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
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

7 authors at 3 institutions in 1 country.

Hong ZhangDepartment of Cell Biology and Molecular Genetics, The University of Maryland, College Park, MD 20742, USA.
Parker MurphyDepartment of Cell Biology and Molecular Genetics, The University of Maryland, College Park, MD 20742, USA.
Jason YuDepartment of Cell Biology and Molecular Genetics, The University of Maryland, College Park, MD 20742, USA.
Sukyeong LeeDepartment of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Francis T F TsaiDepartment of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Ambro van HoofDepartment of Microbiology and Molecular Genetics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Jiqiang LingDepartment of Cell Biology and Molecular Genetics, The University of Maryland, College Park, MD 20742, USA.ORCID 0000-0003-4466-8304
University of Maryland, College Park · USBaylor College of Medicine · USThe University of Texas Health Science Center at Houston · US

Funding

RNAse functions in post-transcriptional gene regulationR35GM141710 · NIGMS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI VAN HOOF, AMBRO · 2021 to 2025
$2.4M
Structure, Function, and Mechanism of a Mitochondrial ChaperoneR01GM142143 · NIGMS · BAYLOR COLLEGE OF MEDICINE · PI TSAI, FRANCIS T.F. · 2021 to 2024
$2.2M
Regulation and Physiological Roles of Translational FidelityR35GM136213 · NIGMS · UNIV OF MARYLAND, COLLEGE PARK · PI LING, JIQIANG · 2020 to 2024
$2.0M
NIGMS NIH HHS R01 GM142143NIGMS NIH HHS R35 GM136213NIGMS NIH HHS R35 GM141710
6 · The paper itself

Abstract

Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes that ligate amino acids to tRNAs, and often require editing to ensure accurate protein synthesis. Recessive mutations in aaRSs cause various neurological disorders in humans, yet the underlying mechanism remains poorly understood. Pathogenic aaRS mutations frequently cause protein destabilization and aminoacylation deficiency. In this study, we report that combined aminoacylation and editing defects cause severe proteotoxicity. We show that the ths1-C268A mutation in yeast threonyl-tRNA synthetase (ThrRS) abolishes editing and causes heat sensitivity. Surprisingly, experimental evolution of the mutant results in intragenic mutations that restore heat resistance but not editing. ths1-C268A destabilizes ThrRS and decreases overall Thr-tRNAThr synthesis, while the suppressor mutations in the evolved strains improve aminoacylation. We further show that deficiency in either ThrRS aminoacylation or editing is insufficient to cause heat sensitivity, and that ths1-C268A impairs ribosome-associated quality control. Our results suggest that aminoacylation deficiency predisposes cells to proteotoxic stress.

Indexed as

Amino Acyl-tRNA SynthetasesProteotoxic StressAminoacylationHumansMutationRNA, TransferSaccharomyces cerevisiaeThreonine-tRNA LigaseAmino Acyl-tRNA SynthetasesRNA, TransferThreonine-tRNA Ligase

Identifiers

PMID37742077
PMCPMC10602869
OpenAlexW4386990213

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.