Genome-wide identification of functional tRNA-derived fragments in Senescence-accelerated mouse prone 8 brain

tRNA-derived fragments (tRFs) have been linked previously to the development of various diseases, such as cancer, viral infectious disease, Parkinson9s disease, and intellectual disability. However, the link between tRFs and Alzheimer9s disease (AD) has not been understood. RNA sequencing, a state-of-the-art technology, has largely increased the level of research on tRFs in AD. In this study, we investigated the changes in tRFs in SAMP8 and SAMR1 mouse brains at 7 months of age. A total of 596 tRF transcripts were discovered. Among these transcripts, 13, including 4 upregulated and 9 downregulated transcripts, were found to be differentially expressed in the SAMP8 mice. Then, we obtained 137 potential target genes through an miRNA-like pathway. Gene Ontology (GO) survey indicated that these target genes are implicated in AD pathogenesis from different aspects, for example, postsynaptic density (GO: 0014069). Furthermore, the tRFs that most likely affect the progression of AD by miRNA-like pattern were estimated and displayed in detail, such as AS-tDR-011775 acted on Mobp immediately and Camk2n1 was targeted by AS-tDR-011389. Actually, the tRFs participated in the regulation of gene expression by means other than the miRNA-like pattern. Therefore, these 13 dysregulated tRFs may hold consequences far into the future and can be attractive biomarkers and valid targets. In brief, our study is the first to provide a comprehensive analysis on tRFs in SAMP8 mouse brain, and this breakthrough identified promising new targets for the therapeutic intervention of AD.