tRF-Val-TAC-004 protects against renal ischemia-reperfusion injury via attenuating Apaf1-mediated apoptosis

tRNA-derived fragments (tRFs) play critical roles in cellular process, and we have previously reported that tRFs are involved in ischemia reperfusion injury induced acute kidney injury (IRI-AKI). However, the precise involvement of tRFs in IRI-AKI remains obscure. This study aims to elucidate the impact of tRF-Val-TAC-004 (tRF-Val) on IRI-AKI and uncover the underlying mechanisms. Our observations reveal a significant downregulation of tRF-Val in IRI-AKI mice and its overexpression mitigated renal dysfunction, morphological damage, and apoptosis in IRI-AKI mice, while its inhibition exacerbated these effects. Similar outcomes were replicated in CoCl₂-treated BUMPT cells upon transfection with tRF-Val mimic or inhibitor. Mechanistically, dual-luciferase reporter assay and AGO-RIP qPCR analyses demonstrated that tRF-Val suppresses Apaf1 expression by targeting the 3'-UTR of <i>Apaf1</i> mRNA. Furthermore, the protective efficacy of tRF-Val was notably weakened by <i>Apaf1</i>-overexpressing plasmids. In summary, these novel findings unveil the protective role of tRF-Val against IRI-AKI through inhibition of Apaf1-mediated apoptosis.