Extracellular vesicles-associated tRNA-derived fragments (tRFs): biogenesis, biological functions, and their role as potential biomarkers in human diseases

Abstract

Traditionally, transfer RNAs (tRNAs) specifically decoded messenger RNA (mRNA) and participated in protein translation. tRNA-derived fragments (tRFs), also known as tRNA-derived small RNAs (tsRNAs), are generated by the specific cleavage of pre- and mature tRNAs and are a class of newly defined functional small non-coding RNAs (sncRNAs). Following the different cleavage positions of precursor or mature tRNA, tRFs are classified into seven types, 5′-tRNA half, 3′-tRNA half, tRF-1, 5′U-tRF, 3′-tRF, 5′-tRF, and i-tRF. It has been demonstrated that tRFs have a diverse range of biological functions in cellular processes, which include inhibiting protein translation, modulating stress response, regulating gene expression, and involvement in cell cycles and epigenetic inheritance. Emerging evidences have indicated that tRFs in extracellular vesicles (EVs) seem to act as regulatory molecules in various cellular processes and play essential roles in cell-to-cell communication. Furthermore, the dysregulation of EV-associated tRFs has been associated with the occurrence and progression of a variety of cancers and they can serve as novel potential biomarkers for cancer diagnosis. In this review, the biogenesis and classification of tRFs are summarized, and the biological functions of EV-associated tRFs and their roles as potential biomarkers in human diseases are discussed.

Distinct non-coding RNA cargo of extracellular vesicles from M1 and M2 human primary macrophages

“…The clinical significance of tRNAs and tRFs in EVs has recently been reviewed by Liu et al (2022) and Weng et al (2022).…”

“…This highlights the need for standardised nomenclature for the different tRFs to enable inter-study comparisons and metanalyses. The clinical significance of tRNAs and tRFs in EVs has recently been reviewed by Liu et al (2022) and Weng et al (2022).…”

Identification of RNA-based cell-type markers for the stem cell manufacture system with a statistical scoring function

“…This type of RNAs, tRNA-derived fragments, are generated by the cleavage of tRNAs. It has been demonstrated that tRNA-derived fragments in extracellular vesicles act as regulatory molecules in various cellular processes and have the potential to be biomarkers in human diseases 43 . SNORD118 was ranked as the fourth top-ranked candidate in all ex-RNAs for hESC cells.…”

“…Fib-iPSCs were obtained from Human Embryonic Stem Cell Core, Harvard Medical School. Fib-iPSCs were reprogrammed from fibroblasts, by George Q. Daley Lab (Children's Hospital Boston, MA) and have been well characterized and described in the literature [43]. For 2D cell culture, H9s and iPSCs were cultured in 6-welll plate coated with Matrigel (BD Biosciences, #354277) in Essential 8 TM medium (E8, Life Technologies, #A1517001).…”

Therapeutic Strategy of Mesenchymal-Stem-Cell-Derived Extracellular Vesicles as Regenerative Medicine

“…The level of EVs in humans has gained attention for the early diagnosis of various diseases using liquid biopsy owing to their distribution in various body fluids, including blood, urine, saliva, spinal fluid, and tears, as well as their stability [ 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 ]. As the amount and type of these functional molecules present within or on the surface of EVs vary depending on the disease, they could be used for disease diagnosis, prognosis, and therapeutic targets [ 108 , 109 , 110 , 111 , 112 , 113 , 114 <...…”