Evidence map›Paper›PMID 34761260›Full record

ArticleNucleic acids research2021

Evolutionary repair reveals an unexpected role of the tRNA modification m1G37 in aminoacylation.

Ben E Clifton, Muhammad A Fariz, Gen-Ichiro Uechi, Paola Laurino

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

14 citing papers in PubMed, 21 citations in OpenAlex.

  1. Compendium of RNA modifications for bacterial stress adaptation.Microbiology and molecular biology reviews : MMBR · 2026
    Review
  2. Specific host translation perturbations promote TnbioRxiv : the preprint server for biology · 2026
    Article
  3. Nicotinamide-Based Covalent Inhibitors of tRNA (mACS medicinal chemistry letters · 2026
    Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. RNA modifying enzymes shape tRNA biogenesis and function.The Journal of biological chemistry · 2024
    Review
  9. Article
  10. Experimental evolution for cell biology.Trends in cell biology · 2023
    Review
  11. Article
  12. Review
  13. Article
  14. Structural and functional characterization of TrmM in mProtein science : a publication of the Protein Society · 2022
    Article
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

4 authors at 1 institution in 1 country.

Ben E CliftonProtein Engineering and Evolution Unit, Okinawa Institute of Science and Technology, Onna, Okinawa 904-0495, Japan.
Muhammad A FarizProtein Engineering and Evolution Unit, Okinawa Institute of Science and Technology, Onna, Okinawa 904-0495, Japan.
Gen-Ichiro UechiProtein Engineering and Evolution Unit, Okinawa Institute of Science and Technology, Onna, Okinawa 904-0495, Japan.
Paola LaurinoProtein Engineering and Evolution Unit, Okinawa Institute of Science and Technology, Onna, Okinawa 904-0495, Japan.ORCID 0000-0002-3725-2645
Okinawa Institute of Science and Technology Graduate University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The tRNA modification m1G37, introduced by the tRNA methyltransferase TrmD, is thought to be essential for growth in bacteria because it suppresses translational frameshift errors at proline codons. However, because bacteria can tolerate high levels of mistranslation, it is unclear why loss of m1G37 is not tolerated. Here, we addressed this question through experimental evolution of trmD mutant strains of Escherichia coli. Surprisingly, trmD mutant strains were viable even if the m1G37 modification was completely abolished, and showed rapid recovery of growth rate, mainly via duplication or mutation of the proline-tRNA ligase gene proS. Growth assays and in vitro aminoacylation assays showed that G37-unmodified tRNAPro is aminoacylated less efficiently than m1G37-modified tRNAPro, and that growth of trmD mutant strains can be largely restored by single mutations in proS that restore aminoacylation of G37-unmodified tRNAPro. These results show that inefficient aminoacylation of tRNAPro is the main reason for growth defects observed in trmD mutant strains and that proS may act as a gatekeeper of translational accuracy, preventing the use of error-prone unmodified tRNAPro in translation. Our work shows the utility of experimental evolution for uncovering the hidden functions of essential genes and has implications for the development of antibiotics targeting TrmD.

Indexed as

MutationRNA Processing, Post-TranscriptionalAdaptation, PhysiologicalAminoacylationDirected Molecular EvolutionEscherichia coliEscherichia coli ProteinsOperonPlasmidsRNA, Transfer, ProtRNA MethyltransferasesEscherichia coli ProteinsRNA, Transfer, ProTrmD protein, E colitRNA Methyltransferases

Identifiers

PMID34761260
PMCPMC8643618
OpenAlexW3213309120

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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.