Evidence map›Paper›PMID 40637226›Full record

ArticleNucleic acids research2025

A tRNA gene potential to activate interferon signaling involves selective termination and is suppressible by La protein/SSB.

Alan C Kessler, Sandy Mattijssen, Gennady H Margolin, Jack Y Prochnau, James R Iben, Tianwei Li, Sergei Gaidamakov, Ian P Schowe, Markus Hafner, Richard J Maraia

Abstract read
In one paragraph

Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

10 authors.

Alan C KesslerSection on Molecular and Cell Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Intramural Research Program, National Institutes of Health, Bethesda, MD 20892, United States.
Sandy MattijssenSection on Molecular and Cell Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Intramural Research Program, National Institutes of Health, Bethesda, MD 20892, United States.ORCID 0000-0002-4285-7438
Gennady H MargolinBioinformatics and Scientific Programming Core, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Intramural Research Program, National Institutes of Health, Bethesda, MD 20892, United States.
Jack Y ProchnauSection on Molecular and Cell Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Intramural Research Program, National Institutes of Health, Bethesda, MD 20892, United States.ORCID 0000-0003-3243-6346
James R IbenMolecular Genomics Core, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Intramural Research Program, National Institutes of Health, Bethesda, MD 20892, United States.
Tianwei LiMolecular Genomics Core, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Intramural Research Program, National Institutes of Health, Bethesda, MD 20892, United States.
Sergei GaidamakovSection on Molecular and Cell Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Intramural Research Program, National Institutes of Health, Bethesda, MD 20892, United States.
Ian P SchoweSection on Molecular and Cell Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Intramural Research Program, National Institutes of Health, Bethesda, MD 20892, United States.ORCID 0009-0000-1021-1547
Markus HafnerRNA Molecular Biology Laboratory, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Intramural Research Program, National Institutes of Health, Bethesda, MD 20892, United States.ORCID 0000-0002-4336-6518
Richard J MaraiaSection on Molecular and Cell Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Intramural Research Program, National Institutes of Health, Bethesda, MD 20892, United States.ORCID 0000-0002-5209-0066

Funding

MOLECULAR REGULATION OF GENE EXPRESSIONZ01HD000412 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI MARAIA, RICHARD J · 1988 to 2008
$1.8M
Eunice Kennedy Shriver National Institute of Child Health and Human Development HD000412-36Intramural NIH HHS Z01 HD000412Intramural Research Program
6 · The paper itself

Abstract

RNA polymerase III (Pol III) and some of its small non-coding RNAs have been co-opted by the immune system. We discovered a non-canonical activity for a human tRNA gene, TRT-TGT4-1, robust activation of interferon-stimulated gene (ISG) response after transfection into HEK293T cells, dependent on Pol III promoter-directed transcription and its flanking sequences. The activity requires the pattern recognition receptor RIG-I, which is activated by short RNAs with 5'-triphosphate (5'ppp). We characterized sequence-specific features of the TRT-TGT4-1 Pol III minimal T(4) terminator element which is uniquely required for and controls its ISG activity. Related, La protein, the Pol III transcript U(n)-3' terminus-binding protein, can promote and/or suppress the activity. Screening identified other tRNA genes with ISG activity whose subsequent analysis revealed the ISG-positive and ISG-negative ones differ most significantly in the 5'-dinucleotides preceding their terminators and T(n) length. Replacing the ISG-positive consensus 5'AC of TRT-TGT4-1 with an ISG-negative terminator 5'GG, markedly decreased termination and ISG activity. The data support a model in which Pol III terminators can channel transcripts and affect their potential for ISG activity or tRNA maturation. The findings reveal insight into other tRNA gene features involved in ISG signaling, and suggest some tRNA genes may express such potential.

Indexed as

InterferonsRibonucleoproteinsRNA, TransferSignal TransductionTranscription Termination, GeneticDEAD Box Protein 58HEK293 CellsHumansPromoter Regions, GeneticReceptors, ImmunologicRNA Polymerase IIISS-B AntigenTerminator Regions, GeneticDEAD Box Protein 58InterferonsReceptors, ImmunologicRibonucleoproteinsRIGI protein, humanRNA Polymerase IIIRNA, TransferSS-B Antigen

Identifiers

PMID40637226
PMCPMC12238852

What Socratic 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 Socratic graph.