tRNA-Derived Small RNAs: Novel Epigenetic Regulators

Simple Summary Cells must synthesize new proteins to maintain its life and tRNA (transfer RNA) is an essential component of the translation process. tRNA-derived small RNA (tsRNA) is a relatively uncharacterized small RNA, derived from enzymatic cleavage of the tRNAs. Accumulating evidences suggest that tsRNA is an abundant, highly modified, dynamically regulated small-RNA and interacts with other types of RNAs or proteins. Moreover, it is abnormally expressed in multiple human diseases including systemic lupus, neurological disorder, metabolic disorder and cancer, implying its diverse function in the initiation or progression of such diseases. In this review, we summarize the classification of tsRNA and its role focused on the epigenetic regulation. Further, we discuss the limitation of current knowledge about the tsRNA and its potential applications. An epigenetic change is a heritable genetic alteration that does not involve any nucleotide changes. While the methylation of specific DNA regions such as CpG islands or histone modifications, including acetylation or methylation, have been investigated in detail, the role of small RNAs in epigenetic regulation is largely unknown. Among the many types of small RNAs, tRNA-derived small RNAs (tsRNAs) represent a class of noncoding small RNAs with multiple roles in diverse physiological processes, including neovascularization, sperm maturation, immune modulation, and stress response. Regarding these roles, several pioneering studies have revealed that dysregulated tsRNAs are associated with human diseases, such as systemic lupus, neurological disorder, metabolic disorder, and cancer. Moreover, recent findings suggest that tsRNAs regulate the expression of critical genes linked with these diseases by a variety of mechanisms, including epigenetic regulation. In this review, we will describe different classes of tsRNAs based on their biogenesis and will focus on their role in epigenetic regulation.