Document Type
Article
Publication Date
9-10-2024
Abstract
Chronic obstructive pulmonary disease (COPD) is the most prevalent lung disease, and macrophages play a central role in the inflammatory response in COPD. We here report a comprehensive characterization of circulating short non-coding RNAs (sncRNAs) in plasma from patients with COPD. While circulating sncRNAs are increasingly recognized for their regulatory roles and biomarker potential in various diseases, the conventional RNA sequencing (RNA-seq) method cannot fully capture these circulating sncRNAs due to their heterogeneous terminal structures. By pre-treating the plasma RNAs with T4 polynucleotide kinase, which converts all RNAs to those with RNA-seq susceptible ends (5′-phosphate and 3′-hydroxyl), we comprehensively sequenced a wide variety of non-microRNA sncRNAs, such as 5′-tRNA halves containing a 2′,3′-cyclic phosphate. We discovered a remarkable accumulation of the 5′-half derived from tRNAValCAC in plasma from COPD patients, whereas the 5′-tRNAGlyGCC half is predominant in healthy donors. Further, the 5′-tRNAValCAC half activates human macrophages via Toll-like receptor 7 and induces cytokine production. Additionally, we identified circulating rRNA-derived fragments that were upregulated in COPD patients and demonstrated their ability to induce cytokine production in macrophages. Our findings provide evidence of circulating, immune-active sncRNAs in patients with COPD, suggesting that they serve as inflammatory mediators in the pathogenesis of COPD.
Recommended Citation
Shigematsu, Megumi; Kawamura, Takuya; Deshpande, Deepak; and Kirino, Yohei, "Immunoactive Signatures of Circulating tRNA- And rRNA-Derived RNAs in Chronic Obstructive Pulmonary Disease" (2024). Computational Medicine Center Faculty Papers. Paper 55.
https://jdc.jefferson.edu/tjucompmedctrfp/55
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Language
English
Included in
Genetic Phenomena Commons, Investigative Techniques Commons, Nucleic Acids, Nucleotides, and Nucleosides Commons, Respiratory Tract Diseases Commons
Comments
This article is the author's final published version in Molecular Therapy Nucleic Acids, Volume 35, Issue 3, September 2024, Article number 102285.
The published version is available at https://doi.org/10.1016/j.omtn.2024.102285.
Copyright © 2024 The Author(s). Published by Elsevier Inc. on behalf of The American Society of Gene and Cell Therapy