Evidence map›Paper›PMID 30007351›Full record

ArticleNucleic acids research2018

Conditional accumulation of toxic tRNAs to cause amino acid misincorporation.

Stephanie M Zimmerman, Yoshiko Kon, Alayna C Hauke, Bianca Y Ruiz, Stanley Fields, Eric M Phizicky

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

19 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
  2. Mistranslating tRNA variants impact the proteome and phosphoproteome ofbioRxiv : the preprint server for biology · 2025
    Article
  3. Article
  4. Article
  5. Mistranslating tRNA variants have anticodon- and sex-specific impacts onbioRxiv : the preprint server for biology · 2024
    Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. 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

6 authors at 3 institutions in 1 country.

Stephanie M ZimmermanDepartment of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
Yoshiko KonDepartment of Biochemistry and Biophysics and Center for RNA Biology, University of Rochester School of Medicine, Rochester, NY 14642, USA.
Alayna C HaukeDepartment of Biochemistry and Biophysics and Center for RNA Biology, University of Rochester School of Medicine, Rochester, NY 14642, USA.
Bianca Y RuizDepartment of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
Stanley FieldsDepartment of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
Eric M PhizickyDepartment of Biochemistry and Biophysics and Center for RNA Biology, University of Rochester School of Medicine, Rochester, NY 14642, USA.
University of Rochester · USUniversity of Washington · USHoward Hughes Medical Institute · US

Funding

TrainingP41GM103533 · NIGMS · UNIVERSITY OF WASHINGTON · PI MACCOSS, MICHAEL · 2012 to 2021
$20.7M
TRNA SPLICINGR01GM052347 · NIGMS · UNIVERSITY OF ROCHESTER · PI Eric M. Phizicky · 1995 to 2026
$9.6M
NIGMS NIH HHS P41 GM103533NIGMS NIH HHS R01 GM052347
6 · The paper itself

Abstract

To develop a system for conditional amino acid misincorporation, we engineered tRNAs in the yeast Saccharomyces cerevisiae to be substrates of the rapid tRNA decay (RTD) pathway, such that they accumulate when RTD is turned off. We used this system to test the effects on growth of a library of tRNASer variants with all possible anticodons, and show that many are lethal when RTD is inhibited and the tRNA accumulates. Using mass spectrometry, we measured serine misincorporation in yeast containing each of six tRNA variants, and for five of them identified hundreds of peptides with serine substitutions at the targeted amino acid sites. Unexpectedly, we found that there is not a simple correlation between toxicity and the level of serine misincorporation; in particular, high levels of serine misincorporation can occur at cysteine residues without obvious growth defects. We also showed that toxic tRNAs can be used as a tool to identify sequence variants that reduce tRNA function. Finally, we generalized this method to another tRNA species, and generated conditionally toxic tRNATyr variants in a similar manner. This method should facilitate the study of tRNA biology and provide a tool to probe the effects of amino acid misincorporation on cellular physiology.

Indexed as

Amino Acid SubstitutionAnticodonProtein BiosynthesisRNA StabilityRNA, Transfer, SerRNA, Transfer, TyrSaccharomyces cerevisiaeSerineTyrosineAnticodonRNA, Transfer, SerRNA, Transfer, TyrSerineTyrosine

Identifiers

PMID30007351
PMCPMC6125640
OpenAlexW2858571940

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.