The role of Transfer RNA-Derived Small RNAs (tsRNAs) in Digestive System Tumors

Abstract

Transfer RNA-derived small RNA(tsRNA) is a type of non-coding tRNA undergoing cleavage by specific nucleases such as Dicer. TsRNAs comprise of tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs). Based on the splicing site within the tRNA, tRFs can be classified into tRF-1, tRF-2, tRF-3, tRF-5, and i-tRF. TiRNAs can be classified into 5'-tiRNA and 3'-tiRNA. Both tRFs and tiRNAs have important roles in carcinogenesis, especially cancer of digestive system. TRFs and tiRNAs can promote cell proliferation and cell cycle progression by regulating the expression of oncogenes, combining with RNA binding proteins such as Y-box binding protein 1 (YBX1) to prevent transcription. Despite many reviews on the basic biological function of tRFs and tiRNAs, few have described their correlation with tumors especially gastrointestinal tumor. This review focused on the relationship of tRFs and tiRNAs with the biological behavior, clinicopathological characteristics, diagnosis, treatment and prognosis of digestive system tumors, and would provide novel insights for the early detection and treatment of digestive system tumors.

Keywords: cancer; digestive system tumors; tRFs; tRNAs; tiRNAs; tsRNAs.

Figure 1

The main classification of tRNA-derived fragments (tRFs) and tRNA halves(tiRNAs). In this figure, the tRFs or tiRNAs were shown the source from tRNAs, according to the color which is the same with tRNAs'.

Figure 2

The naming rules of tRFs and tiRNAs. The name described the tRFs or tiRNAs should contain the type (tRF-5, tRF-3, tRF-1, 5'-tiRNA, 3'-tiRNA), Chromosome number, tRNA number, the amino acid carried and the anticodon carried. The anticodon is the codon which tRNA carried, then this anticodon will be translated into the codon which is matched amino acid. And every tRFs has a name in tRFdb (tRFdatabase), for example, tRF-1001 is Chr10. Trna2-SerTGA and it belongs to tRF-1 type, and the number underline in tRFdb means the type (tRF-5, tRF-3 or tRF-1).

Figure 3

5'-tiRNA could promote the cell survival.ThetsRNAs that were derived from the tRNA also binds to the cytochrome C, which then would bind to the apoptotic protease activating factor 1 (APAF1) to form the apoptotic bodies. And the 5'tiRNA and 3'tiRNA could bind to the cytochrome C to form the ribonucleoprotein complex, inhibit formation and activity of the apoptotic bodies, and stimulate the cellular survival. APAF1, apoptotic protease activating factor 1.

Figure 4

tRF-3 could regulate ribosomal functions. The tRF-3s may specifically bind to TWI12 protein (member of the AGO/PiWi protein family), and recruit Tan1 protein and exoribonuclease XRN2, to form pre-ribosomal RNA splicing complex (TXT), process pre-rRNA during rRNA synthesis, and then regulate translation.

Figure 5

5'-tiRNA could promotethe formation of stress granules (SGs). 5'-tiRNA may replace eIF4F, which is an eukaryotic translation initiation factor, at the mRNA ^m7GTP position, to inhibit translation initiation and produce multiple mRNA protein complexes (mRNPs).Those tiRNA may further bind to the cold shock domain (CSD) of the YBX-1 protein (RNA binding protein) to form 5'-TOG-tiRNA-protein complex and then stimulate production of the stress granules (SGs). SGs, stress granules; YBX-1, Y-Box Binding Protein 1; mRNPs, mRNA protein complexes.