tRNA DERIVED FRAGMENTS

Translational regulation by non-coding RNAs is a mechanism commonly used by cells to fine-tune gene expression. A fragment derived from an archaeal valine tRNA (Val-tRF) has been previously identified to bind the small subunit of the ribosome and inhibit translation in Haloferax volcanii Here, we present three cryo-electron microscopy structures of Val-tRF bound to the small subunit of Sulfolobus acidocaldarius ribosomes at resolutions between 4.02 and 4.53 Å. Within these complexes, Val-tRF was observed to bind to conserved RNA-interacting sites, including the ribosomal decoding center...

tRNA-derived fragments (tRFs) play crucial roles in cancer progression. Among them, tRF-27 has been identified as a key factor in promoting naïve trastuzumab resistance in HER2-positive breast cancer. However, the origin of tRF-27 remains uncertain. In this study, we propose that the upregulated expression of specific cysteine tRNAs may lead to the increased accumulation of tRF-27 in trastuzumab-resistant JIMT1 cells. Mechanistically, the reduced inhibitory H3K27me3 modification at the promoter regions of tRF-27-related tRNA genes in JIMT1 cells, potentially resulting from decreased EZH2 and increased KDM6A activity, may be a critical factor stimulating the transcriptional activity of these tRNA genes...

tsRNAs (tRNA-derived small non-coding RNAs), including tRNA halves (tiRNAs) and tRNA fragments (tRFs), have been implicated in some viral infections, such as respiratory viral infections. However, their involvement in SARS-CoV infection is completely unknown. A comprehensive analysis was performed to determine tsRNA populations in a mouse model of SARS-CoV-infected samples containing the wild-type and attenuated viruses. Data from the Gene Expression Omnibus (GEO) dataset at NCBI (accession ID GSE90624 ) was used for this study...

Mycobacterium tuberculosis (Mtb) infection is among the world's deadliest infectious diseases. Developing effective treatments and biomarkers for tuberculosis requires a deeper understanding of its pathobiology and host responses. Here, we report a comprehensive characterization of circulating short non-coding RNAs (sncRNAs) in plasma samples from Mtb-infected patients. We achieved this by pre-treating plasma RNAs with T4 polynucleotide kinase to convert all RNA ends to those compatible with sncRNA sequencing...

Mitochondrial cristae, infoldings of the mitochondrial inner membrane, undergo aberrant changes in their architecture with age. However, the underlying molecular mechanisms and their contribution to brain aging are largely elusive. Here, we observe an age-dependent accumulation of Glu-5'tsRNA-CTC, a transfer-RNA-derived small RNA (tsRNA), derived from nuclear-encoded tRNAGlu in the mitochondria of glutaminergic neurons. Mitochondrial Glu-5'tsRNA-CTC disrupts the binding of mt-tRNALeu and leucyl-tRNA synthetase2 (LaRs2), impairing mt-tRNALeu aminoacylation and mitochondria-encoded protein translation...

The tsRNAs (tRNA-derived small RNAs) are a novel class of small non-coding RNAs derived from transfer-RNAs. Colon adenocarcinoma (COAD) is the most malignant intestinal tumor. This study focused on the identification and characterization of tsRNA biomarkers in colon adenocarcinomas. Data processing and bioinformatic analyses were performed with the packages of R and Python software. The cell proliferation, migration and invasion abilities were determined by CCK-8 and transwell assays. Luciferase reporter assay was used to test the binding of tsRNA with its target genes...

Transfer RNA-derived small RNAs (tsRNAs) have been shown to be involved in early embryo development and repression of endogenous retroelements in embryos and stem cells. However, it is unknown whether tsRNAs also regulate embryo hatching. In this study, we mined the sequencing data of a previous experiment in which we demonstrated that the microRNA (miRNA) cargo of preimplantation embryonic extracellular vesicles (EVs) influences embryo development. We thus profiled the tsRNA cargo of EVs secreted by blastocysts and non-blastocysts...

Despite the substantial progress in multiple myeloma (MM) therapy nowadays, treatment resistance and disease relapse remain major clinical hindrances. Herein, we have investigated tRNA-derived fragment (tRF) profiles in MM and precursor stages (smoldering MM/sMM; monoclonal gammopathy of undetermined significance/MGUS), aiming to unveil potential MM-related tRFs in ameliorating MM prognosis and risk stratification. Small RNA-seq was performed to profile tRFs in bone marrow CD138+ plasma cells, revealing the significant deregulation of the mitochondrial internal tRFHisGTG (mt-i-tRFHisGTG ) in MM versus sMM/MGUS...

RNA polymerase III (Pol III, POLR3) synthesizes tRNAs and other small non-coding RNAs. Human POLR3 pathogenic variants cause a range of developmental disorders, recapitulated in part by mouse models, yet some aspects of POLR3 deficiency have not been explored. We characterized a human POLR3B :c.1625A>G;p.(Asn542Ser) disease variant that was found to cause mis-splicing of POLR3B . Genome-edited POLR3B 1625A>G HEK293 cells acquired the mis-splicing with decreases in multiple POLR3 subunits and TFIIIB, although display auto-upregulation of the Pol III termination-reinitiation subunit POLR3E ...

Transfer RNAs (tRNAs) are fundamental for both cellular and viral gene expression during viral infection. Moreover, mounting evidence supports a noncanonical role for tRNA cleavage products in the control of gene expression during diverse conditions of stress and infection. We previously reported that infection with the model murine gammaherpesvirus, MHV68, leads to altered tRNA transcription, suggesting that tRNA regulation may play an important role in mediating viral replication or the host response. To better understand how viral infection alters tRNA expression, we combined Ordered Two Template Relay (OTTR) with tRNA-specific bioinformatic software called tRAX to profile full-length tRNAs and fragmented tRNA-derived RNAs (tDRs) during infection with MHV68...

RNA profiling studies have revealed that ∼75% of the human genome is transcribed to RNA but only a meagre fraction of it is translated to proteins. Majority of transcribed RNA constitute a specialized pool of non-coding RNAs. Human genome contains approximately 506 genes encoding a set of 51 different tRNAs, constituting a unique class of non-coding RNAs that not only have essential housekeeping functions as translator molecules during protein synthesis, but have numerous uncharted regulatory functions...

Rationale: Angiogenesis expedites tissue impairment in many diseases, including age-related macular degeneration (AMD), a leading cause of irreversible blindness in elderly. A substantial proportion of neovascular AMD patients, characterized by aberrant choroidal neovascularization (CNV), exhibit poor responses or adverse reactions to anti-VEGF therapy. Herein, we aimed to unveil the function of newly identified transfer RNA-derived small RNA, tRF-Glu-CTC, in the pathology of CNV and determine its potential in inhibiting angiogenesis...

Fragments derived from tRNA, called tRNA-derived small RNAs (tsRNAs), have attracted widespread attention in the past decade. tsRNAs are widespread in prokaryotic and eukaryotic transcriptome, which contains two main types, tRNA-derived fragments (tRFs) and tRNA-derived stress-inducing RNA (tiRNAs), derived from the precursor tRNAs or mature tRNAs. According to differences in the cleavage position, tRFs can be divided into tRF-1, tRF-2, tRF-3, tRF-5, and i-tRF, whereas tiRNAs can be divided into 5'-tiRNA and 3'-tiRNA...

The prevalence of diabetic kidney disease (DKD) is increasing annually. Damage to and loss of podocytes occur early in DKD. tRNA-derived fragments (tRFs), originating from tRNA precursors or mature tRNAs, are associated with various illnesses. In this study, tRFs were identified, and their roles in podocyte injury induced by high-glucose (HG) treatment were explored. High-throughput sequencing of podocytes treated with HG was performed to identify differentially expressed tRFs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed...

Metastasis is a significant clinical challenge responsible for cancer mortality and non-response to treatment. However, the molecular mechanisms driving metastasis remain unclear, limiting the development of efficient diagnostic and therapeutic approaches. Recent breakthroughs in cancer biology have discovered a group of small non-coding RNAs called tRNA-derived fragments (tRFs), which play a critical role in the metastatic behavior of various tumors. tRFs are produced from cleavage modifications of tRNAs and have different functional classes based on the pattern of these modifications...

A new class of noncoding RNAs, tsRNAs are not only abundant in humans but also have high tissue specificity. Recently, an increasing number of studies have explored the correlations between tsRNAs and tumors, showing that tsRNAs can affect biological behaviors of tumor cells, such as proliferation, apoptosis and metastasis, by modulating protein translation, RNA transcription or posttranscriptional regulation. In addition, tsRNAs are widely distributed and stably expressed, which endows them with broad application prospects in diagnosing and predicting the prognosis of tumors, and they are expected to become new biomarkers...

In recent decades, considerable evidence has emerged indicating the involvement of tRNA-derived fragments (tRFs) in cancer progression through various mechanisms. However, the biological effects and mechanisms of tRFs in lung adenocarcinoma (LUAD) remain unclear. In this study, we screen out tRF-29-79, a 5'-tRF derived from tRNAGlyGCC, through profiling the tRF expressions in three pairs of LUAD tissues. We show that tRF-29-79 is down-regulated in LUAD and down-regulation of tRF-29-79 is associated with poorer prognosis...

Introduction - tRNA-derived fragments (tRFs) play an important role in immune responses. To clarify the role of tRFs in autoimmunity we studied circulating tRF-levels in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA), and in a murine model for arthritis. Material and Methods - Circulating tRF-levels were quantified by miR-Q RT-qPCR. tRNA processing and modification enzyme expression was analyzed by RT-qPCR and public transcriptomics data. Results - Significant reduction (up to 3-fold on average) of tRF-levels derived from tRNA-Gly-GCC,CCC, tRNA-Glu-CTC, and tRNA-Val-CAC,AAC was observed in RA patients, whereas tRNA-Glu-CTC and tRNA-Val-CAC,AAC tRFs were found at significantly higher levels (up to 3-fold on average) in PsA patients, compared to healthy controls...

BACKGROUND: The relationship between placental pathology and the maternal syndrome of preeclampsia is incompletely characterized. Mismatch between placental nutrient supply and fetal demands induces stress in the syncytiotrophoblast, the layer of placenta in direct contact with maternal blood. Such stress alters the content and increases the release of syncytiotrophoblast extracellular vesicles (STB-EVs) into the maternal circulation. We have previously shown 5'-tRNA fragments (5'-tRFs) constitute the majority of small RNA in STB-EVs in healthy pregnancy...

In recent years, a population of small RNA fragments derived from non-coding RNAs (sfd-RNAs) has gained significant interest due to its functional and structural resemblance to miRNAs, adding another level of complexity to our comprehension of small-RNA-mediated gene regulation. Despite this, scientists need more tools to test the differential expression of sfd-RNAs since the current methods to detect miRNAs may not be directly applied to them. The primary reasons are the lack of accurate small RNA and ncRNA annotation, the multi-mapping read (MMR) placement, and the multicopy nature of ncRNAs in the human genome...