Role of tRNA derived fragments in renal ischemia–reperfusion injury

BACKGROUND: Ischemia–reperfusion injury (IRI) is one of the major causes of acute kidney injury (AKI). tRNA derived fragments (tRFs/tiRNAs) are groups of small noncoding RNAs derived from tRNAs. To date, the role of tRFs/tiRNAs in renal IRI has not been reported. Herein, we aimed to investigate the involvement of tRFs/tiRNAs in the occurrence and development of ischemia–reperfusion-induced AKI. METHODS: Moderate/severe renal IRI mouse models were established by bilateral renal pedicle clamping. The tRF/tiRNA profiles of healthy controls and moderate/severe IRI-stressed kidney tissues were sequenced by Illumina NextSeq 500. Candidate differentially expressed tiRNAs were further verified by RT-qPCR. Biological analysis was also performed. RESULTS: Overall, 152 tRFs/tiRNAs were differentially expressed in the moderate ischemic injury group compared with the normal control group (FC > 2, p < 0.05), of which 47 were upregulated and 105 were downregulated; in the severe ischemic injury group, 285 tRFs/tiRNAs were differentially expressed (FC > 2, p < 0.05), of which 157 were upregulated, and 128 were downregulated. RT-qPCR determination of eight abundantly expressed tiRNAs was consistent with the sequencing results. Gene Ontology analysis for target genes of the tRFs/tiRNAs showed that the most enriched cell components, molecular functions and biological processes were Golgi apparatus, cytoplasmic vesicles, protein binding, cellular protein localization and multicellular organism development. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these target genes were mainly involved in the natural killer cell mediated cytotoxicity pathway, citrate cycle, and regulation of actin cytoskeleton signaling pathway. CONCLUSION: Our results indicated that tRFs/tiRNAs were involved in renal IRI. These tRFs/tiRNAs may be effective partly via regulation of renal immunity, inflammation and metabolism processes. Candidate genes, including tiRNA-Gly-GCC-003, tiRNA-Lys-CTT-003, and tiRNA-His-GTG-002, might be potential biomarkers and therapeutic targets of ischemia–reperfusion injury-induced acute kidney injury.