tRNA-Derived Small RNA: A Novel Regulatory Small Non-Coding RNA

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.

Keywords: biological function; small non-coding RNA; transfer RNA; transfer RNA-derived small RNA.

Figure 1

Multiple transfer RNA (tRNA) genes in human genome. Numbers of tRNA genes are presented for different amino acids and anticodons. Each graph with different colors indicates a different amino acid. Various isoacceptors (tRNA acceptors that accept the same amino acids) exist for each amino acid. Existence of isodeciders (tRNA genes with the same anticodon but different sequences elsewhere in the tRNA body) for each isoacceptor expands the source of RNAs for generation of diverse tRNA-derived small RNAs (tsRNAs).

Figure 2

The types of tsRNAs are classified by size and sequence location in the tRNA structure. 1-tRNA-derived fragment (tRF) is generated by RNase Z, which cleaves 3′ trailer from pre-ribosomal RNA (rRNA). 2-tRF, which contains the anticodon loop, is generated by unknown ribonuclease. In the case of 3-tRFs and 5-tRFs, the subtypes are determined by size and location of the source. tiRNAs are grouped by whether their source sequences are from the 5′ or 3′ tRNA cleaved by angiogenin (ANG).

Figure 3

The diverse functions and working mechanisms of tsRNAs. It is generally accepted that the tsRNAs regulate a variety of biological processes, including gene expression, translation initiation and elongation, stress granule assembly, ribosome biogenesis, intergenerational inheritance, and apoptosis. miRNA: microRNA; RT: reverse transcription; LTR: long terminal repeat; RISC: RNA-induced silencing complex; PBS: primer binding sites; YB1: Y-box binding protein 1.