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.

Differential Expression Profiles and Function Predictions for tRFs & tiRNAs in Skin Injury Induced by Ultraviolet Irradiation

“…tRF-1 is derived from the 3′ tail sequence of the precursor tRNA, which contains a poly U sequence at the 3′ end. tRF-2, not belonging to tRF-5, tRF-3, or tRF-1, comes primarily from the intermediate region of mature tRNAs ( Goodarzi et al, 2015 ; Wang et al, 2020 ; Yu et al, 2021 ). tRFs & tiRNAs play biological roles through a variety of mechanisms, including interacting with proteins or mRNAs, regulating gene expression, controlling cell cycle, regulating chromatin and epigenetic modifications ( Guzzi et al, 2018 ; Xie et al, 2020 ; Li et al, 2021 ).…”

Endogenous tRNA‐derived small RNA (tRF3‐Thr‐AGT) inhibits ZBP1/NLRP3 pathway‐mediated cell pyroptosis to attenuate acute pancreatitis (AP)

“…Aside from the above ncRNAs, emerging shreds of evidence indicate that a newly identified endogenous transfer RNA (tRNA)‐derived small RNAs (tsRNAs) participate in the regulation of differential diseases and cellular functions. For example, Zhang et al evidence that tsRNAs can be used as potential therapeutic biomarkers for Alzheimer's disease, 24 Luo et al explore the relationship between aberrant tsRNAs expressions and IgA nephropathy development, 25 and other researchers report that tsRNAs participate in the regulation of cancer progression 26,46–48 . However, no literature report the involvement of tsRNAs in regulating AP pathogenesis.…”

“…Recently, a large variety of AP‐associated non‐coding RNAs (ncRNAs) with post‐transcriptional regulation activities are identified, those ncRNAs include long non‐coding RNAs (LncRNAs), 18,19 circular RNAs (circRNAs) 20,21 and microRNAs (miRNAs) 22,23 . In addition to the above ncRNAs, a newly identified endogenous transfer RNA (tRNA)‐derived small RNAs (tsRNAs) are reported to be associated with multiple diseases, such as Alzheimer's disease, 24 IgA nephropathy 25 and tumours 26 . However, the role of tsRNAs in regulating AP pathogenesis has not been investigated.…”

“…As previously reported, the main functions of tRNAs are to transfer the amino acid for gene translation, 27,28 and aside from that, researchers report that tRNAs are fragmented into RNA fragments under some specific conditions. Those RNA fragments are named as tRNA‐derived RNA fragments (tRFs) and half‐tRNAs (tiRNAs), which are able to regulate gene expressions 26,29,30 . In our preliminary work, we screened out a novel tsRNA tRF3‐Thr‐AGT that was closely associated with AP, indicating that this tsRNA might be crucial for AP development.…”

“… 22 , 23 In addition to the above ncRNAs, a newly identified endogenous transfer RNA (tRNA)‐derived small RNAs (tsRNAs) are reported to be associated with multiple diseases, such as Alzheimer's disease, 24 IgA nephropathy 25 and tumours. 26 However, the role of tsRNAs in regulating AP pathogenesis has not been investigated. As previously reported, the main functions of tRNAs are to transfer the amino acid for gene translation, 27 , 28 and aside from that, researchers report that tRNAs are fragmented into RNA fragments under some specific conditions.…”