Integrated transcriptomic analysis identifies tsRNA–mRNA regulatory axis in asthma pathogenesis

Background: Asthma is a complex respiratory disorder with incompletely understood molecular mechanisms. tRNA-derived small RNAs (tsRNAs), a newly discovered class of non-coding RNAs, have been implicated in various diseases, but their role in asthma pathogenesis remains largely unexplored. Methods: < 0.05, |FC| > 1.5), and their target mRNAs were predicted via miRanda and TargetScan. Validation was conducted in an independent cohort (GSE201955). Functional interactions were assessed using a tsRNA-mRNA regulatory network, and key findings were experimentally confirmed in house dust mite (HDM)-stimulated BEAS-2B cells via qRT-PCR and dual-luciferase reporter assays. Results: We identified 58 dysregulated tsRNAs and 961 differentially expressed mRNAs in asthma. A regulatory network revealed 343 negatively correlated tsRNA-mRNA pairs, with 36 hub mRNAs validated in GSE201955. Three candidate tsRNAs (tRF-18-SX73IE03, tRF-22-BZBZOS4Y1, tRF-22-MI7O3B1N4) showed consistent dysregulation in HDM-exposed cells. Mechanistically, tRF-21-Z4NY2V7KE directly suppressed MYBL1 expression, as confirmed by luciferase assays. Conclusions: Our study provides the first comprehensive tsRNA-mRNA regulatory network in asthma, uncovering novel post-transcriptional mechanisms in bronchial epithelial cells. The identified tsRNAs and their targets may be potential biomarkers; moreover, they warrant further investigation as therapeutic targets for asthma.