Evidence map›Paper›PMID 38996458›Full record

ArticleMolecular cell2024

The molecular basis of tRNA selectivity by human pseudouridine synthase 3.

Ting-Yu Lin, Leon Kleemann, Jakub Jeżowski, Dominika Dobosz, Michał Rawski, Paulina Indyka, Grzegorz Ważny, Rahul Mehta, Andrzej Chramiec-Głąbik, Łukasz Koziej and 7 more

Abstract read
In one paragraph

Article in Molecular cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
–field-weighted citation impact
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

20 citing papers in PubMed.

  1. The impact of psuedouridine modification on human tRNA.Biochemical Society transactions · 2026
    Review
  2. Article
  3. Article
  4. Article
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  6. Article
  7. Article
  8. Expandingthe Phenotypic Spectrum ofMolecular syndromology · 2026
    Article
  9. Article
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  11. 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

17 authors.

Ting-Yu LinMałopolska Centre of Biotechnology, Jagiellonian University, 30-387 Kraków, Poland. Electronic address: ting-yu.lin@durham.ac.uk.
Leon KleemannDepartment of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, 3012 Bern, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, 3012 Bern, Switzerland.
Jakub JeżowskiMałopolska Centre of Biotechnology, Jagiellonian University, 30-387 Kraków, Poland; Department of Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Kraków, Poland.
Dominika DoboszMałopolska Centre of Biotechnology, Jagiellonian University, 30-387 Kraków, Poland.
Michał RawskiMałopolska Centre of Biotechnology, Jagiellonian University, 30-387 Kraków, Poland; SOLARIS National Synchrotron Radiation Centre, Jagiellonian University, 30-392 Kraków, Poland.
Paulina IndykaMałopolska Centre of Biotechnology, Jagiellonian University, 30-387 Kraków, Poland; SOLARIS National Synchrotron Radiation Centre, Jagiellonian University, 30-392 Kraków, Poland.
Grzegorz WażnySOLARIS National Synchrotron Radiation Centre, Jagiellonian University, 30-392 Kraków, Poland; Doctoral School of Exact and Natural Sciences, Jagiellonian University, 30-348 Kraków, Poland.
Rahul MehtaMałopolska Centre of Biotechnology, Jagiellonian University, 30-387 Kraków, Poland; Doctoral School of Exact and Natural Sciences, Jagiellonian University, 30-348 Kraków, Poland.
Andrzej Chramiec-GłąbikMałopolska Centre of Biotechnology, Jagiellonian University, 30-387 Kraków, Poland.
Łukasz KoziejMałopolska Centre of Biotechnology, Jagiellonian University, 30-387 Kraków, Poland.
Tristan RanffInstitute of Pharmacy and Molecular Biotechnology, Heidelberg University, 69120 Heidelberg, Germany.
Christian FufezanInstitute of Pharmacy and Molecular Biotechnology, Heidelberg University, 69120 Heidelberg, Germany.
Mateusz WawroDepartment of Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Kraków, Poland.
Jakub KochanDepartment of Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Kraków, Poland.
Joanna BeretaDepartment of Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Kraków, Poland.
Sebastian A LeidelDepartment of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, 3012 Bern, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, 3012 Bern, Switzerland. Electronic address: sebastian.leidel@unibe.ch.
Sebastian GlattMałopolska Centre of Biotechnology, Jagiellonian University, 30-387 Kraków, Poland. Electronic address: sebastian.glatt@uj.edu.pl.

Funding

Swiss National Science Foundation 310030_184947
6 · The paper itself

Abstract

Pseudouridine (Ψ), the isomer of uridine, is ubiquitously found in RNA, including tRNA, rRNA, and mRNA. Human pseudouridine synthase 3 (PUS3) catalyzes pseudouridylation of position 38/39 in tRNAs. However, the molecular mechanisms by which it recognizes its RNA targets and achieves site specificity remain elusive. Here, we determine single-particle cryo-EM structures of PUS3 in its apo form and bound to three tRNAs, showing how the symmetric PUS3 homodimer recognizes tRNAs and positions the target uridine next to its active site. Structure-guided and patient-derived mutations validate our structural findings in complementary biochemical assays. Furthermore, we deleted PUS1 and PUS3 in HEK293 cells and mapped transcriptome-wide Ψ sites by Pseudo-seq. Although PUS1-dependent sites were detectable in tRNA and mRNA, we found no evidence that human PUS3 modifies mRNAs. Our work provides the molecular basis for PUS3-mediated tRNA modification in humans and explains how its tRNA modification activity is linked to intellectual disabilities.

Indexed as

Cryoelectron MicroscopyHydro-LyasesIntramolecular TransferasesPseudouridineRNA, TransferCatalytic DomainHEK293 CellsHumansIntellectual DisabilityModels, MolecularMutationProtein BindingRNA, MessengerSubstrate SpecificityHydro-LyasesIntramolecular TransferasesPseudouridinepseudouridine synthasespseudouridylate synthetaseRNA, MessengerRNA, Transferanticodon stem loopcryo-EM structurePseudo-seqpseudouridine synthasePUS1PUS3transcriptometRNA modification

Identifiers

PMID38996458
PMCPMC11258540

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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.