tRF5–22-SerGCT-1 protects the heart against myocardial injury by targeting MSK1

This study aims to explore the expression profiles and potential functions of tsRNAs in MI. Using a mouse model of MI induced by coronary artery ligation, we used smallRNA array to obtain tsRNAs expression profiles. Reverse transcription quantitative polymerase chain reaction(RT-qPCR), Western Blot, tRF5–22-SerGCT-1 mimics and inhibitors, cell proliferation and apoptosis detection, luciferase reporter assay, and bioinformatics analysis were employed to screen differentially expressed tsRNAs and identify the functions of tsRNAs after MI. A total of 175 significantly different tsRNAs (FC &gt; 1.5, <i>p</i> &lt; 0.05) were identified in MI mice, including 98 upregulated and 77 downregulated tsRNAs. Bioinformatics and target gene prediction revealed that two differentially expressed tsRNAs (5‘tiRNA-34-GlnCTG-4, tRF5–22-SerGCT-1) may be involved in processes like autophagy and apoptosis, as well as in key signaling pathways such as MAPK and autophagy. Further investigation of tRF5–22-SerGCT-1 revealed that its overexpression or inhibition in vitro affected MSK1 levels and cardiomyocytes apoptosis following oxygen–glucose deprivation, providing a protective effect. Dual-luciferase assays confirmed that tRF5–22-SerGCT-1 targets MSK1. We found differentially expressed tsRNAs in MI. In addition, our research showed first that tRF5–22-SerGCT-1 might be involved in the MAPK pathways by targeting the MSK1, modulating apoptosis.