Evidence map›Paper›PMID 22832247›Full record

ArticleRNA biology2012

Translational infidelity-induced protein stress results from a deficiency in Trm9-catalyzed tRNA modifications.

Ashish Patil, Clement T Y Chan, Madhu Dyavaiah, John P Rooney, Peter C Dedon, Thomas J Begley

Open access · bronzeAbstract read
In one paragraph

Article in RNA biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
4.6field-weighted citation impact, top 4% 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

74 citing papers in PubMed, 114 citations in OpenAlex.

  1. Article
  2. Review
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  4. Article
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  8. Article
  9. tRNA modification enzyme-dependent redox homeostasis regulates synapse formation and memory.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  10. Article
  11. Review
  12. tRNA epitranscriptome determines pathogenicity of the opportunistic pathogenProceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. tRNA dysregulation and disease.Nature reviews. Genetics · 2022
    Review
  20. Arsenite toxicity is regulated by queuine availability and oxidation-induced reprogramming of the human tRNA epitranscriptome.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article

14 more citing papers are in PubMed but not listed here.

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 4 institutions in 1 country.

Ashish PatilCancer Research Center, University at Albany, State University of New York, Rensselaer, NY, USA.
Clement T Y Chan
Madhu Dyavaiah
John P Rooney
Peter C Dedon
Thomas J Begley
State University of New York · USCancer Research Center · USCenter for Environmental Health · USMassachusetts Institute of Technology · US

Funding

TOXICOLOGY CORE UNITP30ES002109 · NIEHS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI LEVINE, STUART S · 1985 to 2020
$25.6M
The Roles of Trm9 and tRNA Methylation in the DNA Damage ResponseR01ES015037 · NIEHS · STATE UNIVERSITY OF NEW YORK AT ALBANY · PI BEGLEY, THOMAS J · 2006 to 2010
$2.4M
RNA Modifications as Biomarkers of Environmental Stress and InflammationR01ES017010 · NIEHS · STATE UNIVERSITY OF NEW YORK AT ALBANY · PI BEGLEY, THOMAS J · 2009 to 2013
$2.1M
NIEHS NIH HHS P30 ES002109NIEHS NIH HHS R01 ES015037NIEHS NIH HHS R01 ES017010
6 · The paper itself

Abstract

Correct codon-anticodon pairing promotes translational fidelity, with these interactions greatly facilitated by modified nucleosides found in tRNA. We hypothesized that wobble uridine modifications catalyzed by tRNA methyltransferase 9 (Trm9) are essential for translational fidelity. In support, we have used phenotypic, reporter and protein-based assays to demonstrate increased translational infidelity in trm9Δ Saccharomyces cerevisiae cells. Codon reengineering studies suggest that Trm9-catalyzed tRNA modifications promote fidelity during the translation of specific genes, those rich in arginine and glutamic acid codons from mixed boxes. Using quantitative tRNA modification analysis, we determined that trm9Δ cells are only deficient in 2 of 23 tRNA modifications, with those 2, 5-methoxycarbonylmethyluridine (mcm ( 5) U) and 5-methoxycarbonylmethyl-2-thiouridine (mcm ( 5) s ( 2) U), classified as key determinants of translational fidelity. We also show that in the absence of mcm ( 5) U and mcm ( 5) s ( 2) U, the resulting translational infidelity promotes protein errors and activation of unfolded protein and heat shock responses. These data support a model in which Trm9-catalyzed tRNA modifications promote fidelity during the translation of specific transcripts, with decreased wobble base modification leading to translational infidelity, protein errors and activation of protein stress response pathways.

Indexed as

Protein BiosynthesisRNA Processing, Post-TranscriptionalBase PairingBase SequenceCodonGene Knockout TechniquesGentamicinsPeptide Elongation FactorsProtein Synthesis InhibitorsRibonucleotide ReductasesRNA, TransferSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsStress, PhysiologicaltRNA MethyltransferasesUnfolded Protein Responseantibiotic G 418CodonGentamicinsPeptide Elongation FactorsProtein Synthesis InhibitorsRibonucleotide ReductasesRNA, TransferRnr1 protein, S cerevisiaeSaccharomyces cerevisiae ProteinsTRM9 protein, S cerevisiaetRNA MethyltransferasesYEF3 protein, S cerevisiae

Identifiers

PMID22832247
PMCPMC3495739
OpenAlexW1972120393

What OpenQuestion holds

Textmetadata
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.