Abstract
Deep analysis of next-generation sequencing data unveils numerous small non-coding RNAs with distinct functions. Recently, fragments derived from tRNA, named as tRNA-derived small RNA (tsRNA), have attracted broad attention. There are mainly two types of tsRNAs, including tRNA-derived stress-induced RNA (tiRNA) and tRNA-derived fragment (tRF), which differ in the cleavage position of the precursor or mature tRNA transcript. Emerging evidence has shown that tsRNAs are not merely tRNA degradation debris but have been recognized to play regulatory roles in many specific physiological and pathological processes. In this review, we summarize the biogeneses of various tsRNAs, present the emerging concepts regarding functions and mechanisms of action of tsRNAs, highlight the potential application of tsRNAs in human diseases, and put forward the current problems and future research directions.
Highlights
Transfer RNAs are ubiquitous nucleic acid entities that belong to the most abundant small non-coding RNA, constituting 4–10% of all cellular RNA [1]
Based on the length and cleavage sites of Transfer RNAs (tRNAs), tRNA-derived small RNA (tsRNA) can be divided into two main types: one is stress-induced tRNA fragments, produced by specific cleavage in the anticodon loop of mature tRNAs with 28–36 nts length, which has been named as tRNA-derived stress induced RNA; the other is about 14–30 nts length and derived from the mature or primary tRNAs, which has been named as tRNA-derived fragment
Subsequent studies showed that specific tRNA-derived stress-induced RNA (tiRNA) could assemble into a G-quadruplex-like structure (G4-motif), which is able to competitively bind to eIF4G/eIF4A in the translation initiation complex and inhibit cap-dependent mRNA translation but not the translation of internal ribosome entry sites (IRES)-mediated protein translations which are responsible for cell survival and anti-apoptosis [42,43]
Summary
Transfer RNAs (tRNAs) are ubiquitous nucleic acid entities that belong to the most abundant small non-coding RNA, constituting 4–10% of all cellular RNA [1]. Based on the length and cleavage sites of tRNAs, tsRNAs can be divided into two main types: one is stress-induced tRNA fragments, produced by specific cleavage in the anticodon loop of mature tRNAs with 28–36 nts length, which has been named as tRNA-derived stress induced RNA (tiRNA); the other is about 14–30 nts length and derived from the mature or primary tRNAs, which has been named as tRNA-derived fragment (tRF). Both types of tsRNA can accumulate during different biological processes in several species and have very different biogenesis pathways that are slowly being uncovered. The modifications and conformations of mature tRNAs are necessary for the maintenance of tRNA structure and the blockage of endonuclease cleavage, suggesting tsRNAs (especially tiRNA) are likely derived from tRNAs that are not properly modified or folded
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