Evidence map›Paper›PMID 24550462›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

Hydroxylation of the eukaryotic ribosomal decoding center affects translational accuracy.

Christoph Loenarz, Rok Sekirnik, Armin Thalhammer, Wei Ge, Ekaterina Spivakovsky, Mukram M Mackeen, Michael A McDonough, Matthew E Cockman, Benedikt M Kessler, Peter J Ratcliffe and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.

0numbers the graph read from it
0cells of the map it votes in
84citing papers in PubMed
7.1field-weighted citation impact, top 2% 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

84 citing papers in PubMed, 124 citations in OpenAlex.

  1. Article
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  7. Time-resolved NMR detection of prolyl-hydroxylation in intrinsically disordered region of HIF-1α.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  8. Review
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  10. The Involvement ofBiology · 2024
    Article
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  14. Article
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  17. A Ribosomal Perspective on Neuronal Local Protein Synthesis.Frontiers in molecular neuroscience · 2022
    Review
  18. Bacterial translation machinery for deliberate mistranslation of the genetic code.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  19. Article
  20. Review

24 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

12 authors at 1 institution in 1 country.

Christoph LoenarzChemistry Research Laboratory and Oxford Centre for Integrative Systems Biology, University of Oxford, Oxford OX1 3TA, United Kingdom.
Rok Sekirnik
Armin Thalhammer
Wei Ge
Ekaterina Spivakovsky
Mukram M Mackeen
Michael A McDonough
Matthew E Cockman
Benedikt M Kessler
Peter J Ratcliffe
Alexander Wolf
Christopher J Schofield
University of Oxford · GB

Funding

Biotechnology and Biological Sciences Research CouncilCancer Research UKWellcome Trust
6 · The paper itself

Abstract

The mechanisms by which gene expression is regulated by oxygen are of considerable interest from basic science and therapeutic perspectives. Using mass spectrometric analyses of Saccharomyces cerevisiae ribosomes, we found that the amino acid residue in closest proximity to the decoding center, Pro-64 of the 40S subunit ribosomal protein Rps23p (RPS23 Pro-62 in humans) undergoes posttranslational hydroxylation. We identify RPS23 hydroxylases as a highly conserved eukaryotic subfamily of Fe(II) and 2-oxoglutarate dependent oxygenases; their catalytic domain is closely related to transcription factor prolyl trans-4-hydroxylases that act as oxygen sensors in the hypoxic response in animals. The RPS23 hydroxylases in S. cerevisiae (Tpa1p), Schizosaccharomyces pombe and green algae catalyze an unprecedented dihydroxylation modification. This observation contrasts with higher eukaryotes, where RPS23 is monohydroxylated; the human Tpa1p homolog OGFOD1 catalyzes prolyl trans-3-hydroxylation. TPA1 deletion modulates termination efficiency up to ∼10-fold, including of pathophysiologically relevant sequences; we reveal Rps23p hydroxylation as its molecular basis. In contrast to most previously characterized accuracy modulators, including antibiotics and the prion state of the S. cerevisiae translation termination factor eRF3, Rps23p hydroxylation can either increase or decrease translational accuracy in a stop codon context-dependent manner. We identify conditions where Rps23p hydroxylation status determines viability as a consequence of nonsense codon suppression. The results reveal a direct link between oxygenase catalysis and the regulation of gene expression at the translational level. They will also aid in the development of small molecules altering translational accuracy for the treatment of genetic diseases linked to nonsense mutations.

Indexed as

ChlorophytaCodon, TerminatorHumansHydroxylationMass SpectrometryOxygenasesProtein BiosynthesisProtein Processing, Post-TranslationalRibosomal ProteinsRibosomesSaccharomyces cerevisiaeSchizosaccharomycesSpecies SpecificityCodon, TerminatorOxygenasesRibosomal ProteinsRPS23 protein, human2-oxoglutarate oxygenasehypoxianonsense readthroughribosomal hydroxylationtranslation

Identifiers

PMID24550462
PMCPMC3964080
OpenAlexW2003521251

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.