Publikationsdatenbank

Infection-induced 5'-half molecules of tRNA^HisGUGactivate toll-like receptor 7 (2020)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Pawar, Kamlesh

Shigematsu, Megumi

Sharbati, Soroush (WE 3)

Kirino, Yohei

Quelle

PLoS biology

Bandzählung: 18

Heftzählung: 12

Seiten: Artikel e3000982

ISSN: 1544-9173

Sprache

Englisch

Verweise

URL (Volltext): https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000982

DOI: 10.1371/journal.pbio.3000982

Pubmed: 33332353

Kontakt

Institut für Veterinär-Biochemie

Oertzenweg 19 b
14163 Berlin
+49 30 838 62225
biochemie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.