Abstract
Simple SummaryCells 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.
Highlights
Progress in next-generation sequencing technologies has led to the rapid identification and study of various types of small RNAs [1]
Type II Transfer RNAs (tRNAs)-derived small RNAs (tsRNAs) are thought to be generated in the nucleus, it has been reported that a type II tsRNA, tRNA-derived fragments (tRFs)-1001, is generated in the cytoplasm by ELAC2, a tRNA 30 -endonuclease encoded by a prostate cancer susceptibility gene [4,66]
3′tsRNAs are required for the nuclear import of Twi12. These findings demonstrate that tsRNAs are novel protein-interacting RNA (piRNA) and that tsRNA-PIWI complexes play a role in RNA metabolism in the nucleus (Figure 2A) [89]
Summary
Progress in next-generation sequencing technologies has led to the rapid identification and study of various types of small RNAs [1]. Accumulating evidence indicates that tsRNAs play a key role in several processes other than translation; these include maintenance of mRNA stability [16,17], gene silencing [5,18], reverse transcription [19], and gene regulation [20] These biochemical functions are expected to affect diverse cellular phenotypes. With the improvement of accurate detection methods, the tsRNA is anticipated to be used as a diagnostic or prognostic biomarker for various human diseases With this accumulating information regarding tsRNAs, there are critical points that should be further investigated to fully understand the mechanisms of action of these versatile small RNAs. First, there are only few known nucleases that cleave tRNAs, including angiogenin [23], RNase. Changes in DNA methylation patterns are essential for cancer cell survival [48] These findings highlight the critical role of epigenetic regulation in cancer development. We summarize the current knowledge on the classification and biogenesis of tsRNAs and on the epigenetic mechanisms involving tsRNAs and their potential applications
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