The potential role of tRNAs and small RNAs derived from tRNAs in the occurrence and development of systemic lupus erythematosus

Abstract

Background: Emerging evidence has shown the involvement of dysregulated transfer RNAs (tRNAs) and small RNAs derived from transfer RNAs (tsRNAs) in the pathophysiology of human diseases. The role of tRNAs and tsRNAs in systemic lupus erythematosus (SLE) remains unclear. Therefore, this study aims to investigate the possible regulatory roles of tRNAs and tsRNAs in the pathological mechanism of SLE.

Methods: Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) of 20 SLE patients and 20 normal controls (NCs) to obtain tRNAs and tsRNAs, followed by tRNA and tsRNA expression profiling by the NextSeq system. Target genes were predicted by informatics analysis. Subsequently, to explore the function of messenger RNA (mRNA) in these target genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using the Cytoscape plug-in BinGo, the DAVID database, and Cytoscape software.

Results: A total of 101 tRNAs and 355 tsRNAs were found to be differentially expressed in SLE patients versus NCs by RNA microarray. GO analysis revealed that the altered target genes of the selected tRNAs and tsRNAs were most enriched similarly in immune response and the immune system process. Moreover, KEGG pathway analysis demonstrated that altered target genes of tRNAs were most enriched in systemic lupus erythematosus, while the altered target genes of tsRNAs were most enriched in the T cell receptor signalling pathway, Th1 and Th2 cell differentiation and primary immunodeficiency. These pathways may be related to the initiation of SLE.

Conclusion: Our results provide a novel perspective for studying the tRNA-related and tsRNA-related pathogenesis of SLE.

Keywords: Bioinformatics; Systemic lupus erythematosus; tRF; tRNA; tiRNA.