tsRNA modifications: An emerging layer of biological regulation in disease

Transfer RNA (tRNA)-derived small RNA (tsRNA) represents an important and increasingly valued type of small non-coding RNA (sncRNA). The investigation of tRNA and tsRNA modification crosswalks has not only provided novel insights into the information and functions of tsRNA, but has also expanded the diversity and complexity of the tsRNA biological regulation network. Comparing with other sncRNAs, tsRNA biogenesis show obvious correlation with RNA modifications from mature tRNA and harbor various tRNA modifications. In this review, we aim to present the current aspect of tsRNA modifications and that modified tsRNA shape different regulatory mechanisms in physiological and pathological processes. Strategies for studying tsRNA mechanisms include its specific generation and functional effects induced by sequence/RNA modification/secondary structure. tsRNAs could harbor more than one tRNA modifications such as 5-methylcytosine (mC), N1-methyladenosine (mA), pseudouridine (Ψ) and N7-methylguanosine (mG). This review consolidates the current knowledge of tRNA modification regulating tsRNA biogenesis, outlines the functional roles of various modified tsRNA and highlights their specific contributions in various disease pathogenesis. Therefore, the improvement of tsRNA modification detection technology and the introduction of experimental methods of tsRNA modification are conducive to further broadening the understanding of tsRNA function at the level of RNA modification.