Evidence map›Paper›PMID 30102387›Full record

ArticleNucleic acids research2018

Double methylation of tRNA-U54 to 2'-O-methylthymidine (Tm) synergistically decreases immune response by Toll-like receptor 7.

Patrick Keller, Isabel Freund, Virginie Marchand, Guillaume Bec, Raven Huang, Yuri Motorin, Tatjana Eigenbrod, Alexander Dalpke, Mark Helm

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 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.0field-weighted citation impact, top 24% 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

22 citing papers in PubMed, 30 citations in OpenAlex.

  1. Review
  2. tRNA modifications in viral replication.The Journal of biological chemistry · 2026
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  12. The tRNAProceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  13. Review
  14. Article
  15. Synthesis of point-modified mRNA.Nucleic acids research · 2022
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  16. Review
  17. Review
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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

9 authors at 5 institutions in 3 countries.

Patrick KellerInstitute of Pharmacy and Biochemistry, Johannes Gutenberg-University of Mainz, Staudingerweg 5, D-55128 Mainz, Germany.
Isabel FreundDepartment of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg University Hospital, 69120 Heidelberg, Germany.
Virginie MarchandNext Generation Sequencing Platform, UMS2008 Ingénierie Biologie Santé en Lorraine (IBSLor), BioPôle de l'Université de Lorraine Campus Biologie-Santé, 9, avenue de la Forêt de Haye, CS 50184, 54505 Vandoeuvre-les-Nancy, France.
Guillaume BecBiophysics and Structural Biology Team, Unité Architecture et réactivité de l'ARN (UPR9002), Institut de Biologie Moléculaire et Cellulaire du CNRS, Université de Strasbourg, 15, rue René Descartes, F67084, Strasbourg cedex, France.
Raven HuangDepartment of Biochemistry, Center for Biophysics & Computational Biology, University of Illinois at Urbana-Champaign, 411 Roger Adams Lab., 600 S. Mathews Ave. Urbana, IL 61801, USA.
Yuri MotorinLaboratoire Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA) UMR7365 CNRS-UL, BioPôle de l'Université de Lorraine Campus Biologie-Santé, 9, avenue de la Forêt de Haye, CS 50184, 54505 Vandoeuvre-les-Nancy, France.
Tatjana EigenbrodDepartment of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg University Hospital, 69120 Heidelberg, Germany.
Alexander DalpkeDepartment of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg University Hospital, 69120 Heidelberg, Germany.
Mark HelmInstitute of Pharmacy and Biochemistry, Johannes Gutenberg-University of Mainz, Staudingerweg 5, D-55128 Mainz, Germany.
Heidelberg University · DECentre National de la Recherche Scientifique · FRJohannes Gutenberg University Mainz · DEUniversité de Lorraine · FRUniversity of Illinois Urbana-Champaign · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Sensing of nucleic acids for molecular discrimination between self and non-self is a challenging task for the innate immune system. RNA acts as a potent stimulus for pattern recognition receptors including in particular human Toll-like receptor 7 (TLR7). Certain RNA modifications limit potentially harmful self-recognition of endogenous RNA. Previous studies had identified the 2'-O-methylation of guanosine 18 (Gm18) within tRNAs as an antagonist of TLR7 leading to an impaired immune response. However, human tRNALys3 was non-stimulatory despite lacking Gm18. To identify the underlying molecular principle, interferon responses of human peripheral blood mononuclear cells to differentially modified tRNALys3 were determined. The investigation of synthetic modivariants allowed attributing a significant part of the immunosilencing effect to the 2'-O-methylthymidine (m5Um) modification at position 54. The effect was contingent upon the synergistic presence of both methyl groups at positions C5 and 2'O, as shown by the fact that neither Um54 nor m5U54 produced any effect alone. Testing permutations of the nucleobase at ribose-methylated position 54 suggested that the extent of silencing and antagonism of the TLR7 response was governed by hydrogen patterns and lipophilic interactions of the nucleobase. The results identify a new immune-modulatory endogenous RNA modification that limits TLR7 activation by RNA.

Indexed as

GuanosineHumansHydrogenImmunity, InnateInterferonsLeukocytes, MononuclearMethylationNucleic AcidsRNA, TransferThymidineToll-Like Receptor 72'-O-methylthymidineGuanosineHydrogenInterferonsNucleic AcidsRNA, TransferThymidineTLR7 protein, humanToll-Like Receptor 7

Identifiers

PMID30102387
PMCPMC6182150
OpenAlexW2887650798

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.