tRNA derived small RNAs—Small players with big roles

Abstract

In the past 2 decades, small non-coding RNAs derived from tRNA (tsRNAs or tRNA derived fragments; tRFs) have emerged as new powerful players in the field of small RNA mediated regulation of gene expression, translation, and epigenetic control. tRFs have been identified from evolutionarily divergent organisms from Archaea, the higher plants, to humans. Recent studies have confirmed their roles in cancers and other metabolic disorders in humans and experimental models. They have been implicated in biotic and abiotic stress responses in plants as well. In this review, we summarize the current knowledge on tRFs including types of tRFs, their biogenesis, and mechanisms of action. The review also highlights recent studies involving differential expression profiling of tRFs and elucidation of specific functions of individual tRFs from various species. We also discuss potential considerations while designing experiments involving tRFs identification and characterization and list the available bioinformatics tools for this purpose.

Expression profiles of tRNA‑derived fragments in high glucose‑treated tubular epithelial cells

“…With advances in next-generation sequencing technology, numerous sncRNAs, including microRNAs, circular, p-element-induced wimpy testis-interacting and small nucleolar RNAs and tRNAs, have been confirmed to serve significant roles in a variety of diseases (27). Recently, tRNA-derived small fragments, called tsRNAs, have attracted considerable attention (28)(29)(30). The two types of tsRNA, tRNA-derived stress-induced RNA (tiRNA) and tRFs, are classified according to the different cleavage positions of the precursor or mature tRNA transcript (31).…”

tRNA-derived small RNAs in human cancers: roles, mechanisms, and clinical application

“…Although the functions of tsRNAs have not yet been elucidated, an increasing number of studies have shown that tsRNAs play their biological functions in multiple regulatory mechanism, including epigenetic regulation, transcriptional or post-transcriptional regulation, and translation regulation [ 66 ] (Fig. 3 ).…”

Small RNA‐seq and clinical evaluation of tRNA‐derived fragments in multiple myeloma: Loss of mitochondrial i‐tRFHisGTG results in patients' poor treatment outcome

“…tRFs play pivotal roles in regulating gene expression, acting in a miRNA-like manner and affecting numerous biological processes, including cell proliferation, migration and apoptosis. 15,16 Interestingly, a substantial proportion of tRFs arises from mitochondrial tRNAs (mt-tRNAs) and are actively implicated in tumorigenesis and cancer progression, primarily through their role in perturbing translation and mitochondrial metabolism. 17,18 Herein, we have investigated tRF profiles in association with MM and benign disease states (MGUS/sMM), aiming to reveal potential MM-related tRFs of clinical significance.…”

“…Although tRFs were considered as by‐products of tRNA metabolism, recent studies and high‐throughput sequencing techniques have brought them to RNA biology spotlight regarding their distinct evolutionary conserved sequences and high abundance in various cell types. tRFs play pivotal roles in regulating gene expression, acting in a miRNA‐like manner and affecting numerous biological processes, including cell proliferation, migration and apoptosis 15,16 . Interestingly, a substantial proportion of tRFs arises from mitochondrial tRNAs (mt‐tRNAs) and are actively implicated in tumorigenesis and cancer progression, primarily through their role in perturbing translation and mitochondrial metabolism 17,18 …”