Evidence map›Paper›PMID 33332353›Full record

ArticlePLoS biology2020

Infection-induced 5'-half molecules of tRNAHisGUG activate Toll-like receptor 7.

Kamlesh Pawar, Megumi Shigematsu, Soroush Sharbati, Yohei Kirino

Open access · goldAbstract read
In one paragraph

Article in PLoS biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed, 2 pooled it
2.9field-weighted citation impact, top 8% 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

62 citing papers in PubMed, 2 syntheses or guidelines pooled it, 109 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Article
  5. Review
  6. Review
  7. Article
  8. Dissecting the small RNA code of inflammatory bowel disease.Molecular medicine (Cambridge, Mass.) · 2026
    Article
  9. Article
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  11. Article
  12. Y-box binding proteins in immunity and RNA virus infection.Microbiology and molecular biology reviews : MMBR · 2025
    Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Emerging roles of transfer RNA fragments in the CNS.Brain : a journal of neurology · 2025
    Review
  19. Article
  20. Article

2 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

4 authors at 2 institutions in 2 countries.

Kamlesh PawarComputational Medicine Center, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.ORCID 0000-0002-9767-0152
Megumi ShigematsuComputational Medicine Center, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
Soroush SharbatiInstitute of Veterinary Biochemistry, Department of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.ORCID 0000-0003-3338-7654
Yohei KirinoComputational Medicine Center, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.ORCID 0000-0001-5232-4742
Thomas Jefferson University · USFreie Universität Berlin · DE

Funding

piRNA biogenesis ruled by PIWI-TUDOR interactionR01GM106047 · NIGMS · THOMAS JEFFERSON UNIVERSITY · PI KIRINO, YOHEI · 2013 to 2022
$2.8M
tRNA-derived non-coding RNAs in ASM function and in asthmaR01HL150560 · NHLBI · THOMAS JEFFERSON UNIVERSITY · PI DESHPANDE, DEEPAK A, KIRINO, YOHEI · 2020 to 2023
$2.4M
Role of proinflammatory tRNA-derived RNAs in asthmaR21AI130496 · NIAID · THOMAS JEFFERSON UNIVERSITY · PI KIRINO, YOHEI · 2017 to 2018
$429k
Role of Toll-like receptor-induced short non-coding RNAs in innate immune responseR21AI151641 · NIAID · THOMAS JEFFERSON UNIVERSITY · PI KIRINO, YOHEI · 2021 to 2022
$429k
NHLBI NIH HHS R01 HL150560NIAID NIH HHS R21 AI130496NIAID NIH HHS R21 AI151641NIGMS NIH HHS R01 GM106047
6 · The paper itself

Abstract

Toll-like receptors (TLRs) play a crucial role in the innate immune response. Although endosomal TLR7 recognizes single-stranded RNAs, their endogenous RNA ligands have not been fully explored. Here, we report 5'-tRNA half molecules as abundant activators of TLR7. Mycobacterial infection and accompanying surface TLR activation up-regulate the expression of 5'-tRNA half molecules in human monocyte-derived macrophages (HMDMs). The abundant accumulation of 5'-tRNA halves also occur in HMDM-secreted extracellular vehicles (EVs); the abundance of EV-5'-tRNAHisGUG half molecules is >200-fold higher than that of the most abundant EV-microRNA (miRNA). Sequence identification of the 5'-tRNA halves using cP-RNA-seq revealed abundant and selective packaging of specific 5'-tRNA half species into EVs. The EV-5'-tRNAHisGUG half was experimentally demonstrated to be delivered into endosomes in recipient cells and to activate endosomal TLR7. Up-regulation of the 5'-tRNA half molecules was also observed in the plasma of patients infected with Mycobacterium tuberculosis. These results unveil a novel tRNA-engaged pathway in the innate immune response and assign the role of "immune activators" to 5'-tRNA half molecules.

Indexed as

EndosomesExtracellular VesiclesGene Expression RegulationHumansImmunity, InnateMacrophagesRNA, TransferRNA, Transfer, HisTHP-1 CellsToll-Like Receptor 7RNA, TransferRNA, Transfer, HisTLR7 protein, humanToll-Like Receptor 7

Identifiers

PMID33332353
PMCPMC7745994
OpenAlexW3111508639

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.