Document Type
Article
Publication Date
12-17-2020
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.
Recommended Citation
Pawar, Kamlesh; Shigematsu, Megumi; Sharbati, Soroush; and Kirino, Yohei, "Infection-induced 5'-half molecules of tRNAHisGUG activate Toll-like receptor 7." (2020). Computational Medicine Center Faculty Papers. Paper 30.
https://jdc.jefferson.edu/tjucompmedctrfp/30
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
33332353
Language
English
Comments
This article is the author’s final published version in PLoS Biology, Volume 18, Issue 12, December 2020, Article number e3000982.
The published version is available at https://doi.org/10.1371/journal.pbio.3000982. Copyright © Pawar et al.