Evidence map›Paper›PMID 29596413›Full record

ArticlePLoS genetics2018

Lack of 2'-O-methylation in the tRNA anticodon loop of two phylogenetically distant yeast species activates the general amino acid control pathway.

Lu Han, Michael P Guy, Yoshiko Kon, Eric M Phizicky

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
3.5field-weighted citation impact, top 6% 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

40 citing papers in PubMed, 60 citations in OpenAlex.

  1. Article
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  7. Article
  8. Article
  9. Review
  10. RNA modifying enzymes shape tRNA biogenesis and function.The Journal of biological chemistry · 2024
    Review
  11. Article
  12. Article
  13. The life and times of a tRNA.RNA (New York, N.Y.) · 2023
    Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Article
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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

4 authors at 2 institutions in 1 country.

Lu HanDepartment of Biochemistry and Biophysics, Center for RNA Biology, University of Rochester School of Medicine, Rochester, NY, United States of America.ORCID 0000-0001-6847-2993
Michael P GuyDepartment of Biochemistry and Biophysics, Center for RNA Biology, University of Rochester School of Medicine, Rochester, NY, United States of America.
Yoshiko KonDepartment of Biochemistry and Biophysics, Center for RNA Biology, University of Rochester School of Medicine, Rochester, NY, United States of America.
Eric M PhizickyDepartment of Biochemistry and Biophysics, Center for RNA Biology, University of Rochester School of Medicine, Rochester, NY, United States of America.ORCID 0000-0002-5095-6583
University of Rochester · USNorthern Kentucky University · US

Funding

TRNA SPLICINGR01GM052347 · NIGMS · UNIVERSITY OF ROCHESTER · PI Eric M. Phizicky · 1995 to 2026
$9.6M
NIGMS NIH HHS R01 GM052347NIH HHS GM052347
6 · The paper itself

Abstract

Modification defects in the tRNA anticodon loop often impair yeast growth and cause human disease. In the budding yeast Saccharomyces cerevisiae and the phylogenetically distant fission yeast Schizosaccharomyces pombe, trm7Δ mutants grow poorly due to lack of 2'-O-methylation of C32 and G34 in the tRNAPhe anticodon loop, and lesions in the human TRM7 homolog FTSJ1 cause non-syndromic X-linked intellectual disability (NSXLID). However, it is unclear why trm7Δ mutants grow poorly. We show here that despite the fact that S. cerevisiae trm7Δ mutants had no detectable tRNAPhe charging defect in rich media, the cells constitutively activated a robust general amino acid control (GAAC) response, acting through Gcn2, which senses uncharged tRNA. Consistent with reduced available charged tRNAPhe, the trm7Δ growth defect was suppressed by spontaneous mutations in phenylalanyl-tRNA synthetase (PheRS) or in the pol III negative regulator MAF1, and by overexpression of tRNAPhe, PheRS, or EF-1A; all of these also reduced GAAC activation. Genetic analysis also demonstrated that the trm7Δ growth defect was due to the constitutive robust GAAC activation as well as to the reduced available charged tRNAPhe. Robust GAAC activation was not observed with several other anticodon loop modification mutants. Analysis of S. pombe trm7 mutants led to similar observations. S. pombe Trm7 depletion also resulted in no observable tRNAPhe charging defect and a robust GAAC response, and suppressors mapped to PheRS and reduced GAAC activation. We speculate that GAAC activation is widely conserved in trm7 mutants in eukaryotes, including metazoans, and might play a role in FTSJ1-mediated NSXLID.

Indexed as

AnticodonAmino AcidsGenes, FungalMethylationMutationPhylogenyRNA, TransferSaccharomyces cerevisiaeSchizosaccharomycesAmino AcidsAnticodonRNA, Transfer

Identifiers

PMID29596413
PMCPMC5892943
OpenAlexW2794635962

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.