An old friend with a new face: tRNA-derived small RNAs with big regulatory potential in cancer biology

Abstract

Transfer RNAs (tRNAs) are small non-coding RNAs (sncRNAs) essential for protein translation. Emerging evidence suggests that tRNAs can also be processed into smaller fragments, tRNA-derived small RNAs (tsRNAs), a novel class of sncRNAs with powerful applications and high biological relevance to cancer. tsRNAs biogenesis is heterogeneous and involves different ribonucleases, such as Angiogenin and Dicer. For many years, tsRNAs were thought to be just degradation products. However, accumulating evidence shows their roles in gene expression: either directly via destabilising the mRNA or the ribosomal machinery, or indirectly via regulating the expression of ribosomal components. Furthermore, tsRNAs participate in various biological processes linked to cancer, including apoptosis, cell cycle, immune response, and retroviral insertion into the human genome. It is emerging that tsRNAs have significant therapeutic potential. Endogenous tsRNAs can be used as cancer biomarkers, while synthetic tsRNAs and antisense oligonucleotides can be employed to regulate gene expression. In this review, we are recapitulating the regulatory roles of tsRNAs, with a focus on cancer biology.

Differential Expression of 5’-tRNA Fragments in Circulating Preeclampsia Syncytiotrophoblast Vesicles Drives Macrophage Inflammation

“…Our sequencing approach detected 5'-tRF with hydroxyl groups, but not 2-3 cyclic phosphate residues, suggesting STB-EV 5'-tRFs were generated by ribonucleases other than angiogenin 34 . 5'-tRFs are known to influence cellular function through a variety of regulatory mechanisms at the level of the transcriptome, translatome and the epigenome 15 . We found 5'-tRF-Glu-CTC directly activated macrophages, but not monocytes or umbilical vein endothelial cells.…”

“…EV-bound preeclampsia-upregulated 5'-tRF promote macrophage, but not monocyte activation 5'-tRF can influence cellular function through a wide-range of regulatory mechanisms at the level of transcription, translation and the epigenome 24 . Vascular inflammation is a key feature of preeclampsia 34 .…”

“…There is evidence for a variety of regulatory functions for 5'-tRF 24 . This includes binding argonaute proteins to regulate mRNA stability and affecting components of the ribosomal machinery to impact translation.…”

“…5'-tRF expression profiles can be complex; at least 417 tRNA genes can be cleaved at multiple loci 20 . 5'-tRF are also multifaceted signalling molecules, regulating transcription, translation and epigenetic inheritance [21][22][23][24] . 5'-tRF have mostly been investigated in cancer biology and immunology where they are described as intracellular, autocrine and paracrine signals 19,25,26 .…”

Differential 5′-tRNA Fragment Expression in Circulating Preeclampsia Syncytiotrophoblast Vesicles Drives Macrophage Inflammation

“…14 5ʹ-tRFs are also multifaceted signaling molecules, regulating transcription, translation, and epigenetic inheritance. 15 5ʹ-tRFs have mostly been investigated in cancer biology and immunology, where they are described as intracellular, autocrine, and paracrine signals. 13,16,17 5ʹ-tRFs are stress signals; syncytiotrophoblast stress is a key feature of preeclampsia.…”