Similar Datasets
Project description:How mitochondrial DNA (mtDNA) polymorphisms influence complex phenotypes remains poorly understood. Using Mitochondrial-Nuclear eXchange (MNX) mice, we previously showed that mtDNA single nucleotide polymorphisms (SNP) modify metastasis, cardiovascular disease, and epigenetic marks independently of metabolic differences, suggesting a role for non-protein-coding loci. The only SNP correlating with these phenotypes resides in the gene encoding mitochondrial tRNA-Arginine (mt-tRNAArg (UCG), mt-TR). Here we identify and preliminarily characterize previously undescribed tRNA-derived fragments (tRF) generated from mt-TR. Northern blotting revealed distinct tRF that are differentially expressed between lung and liver and between sexes. Small RNA sequencing failed to capture these tRF unless samples were pre-treated to enzymatically remove non-canonical RNA termini and base methylation. Focusing on fragments with complete homology to mt-TR, the two most abundant tRF align uniquely to the mitochondrial genome and share conserved cleavage sites. Together, these findings uncover mitochondrial-derived tRF as a previously unrecognized small RNA metastasis modifiers and expand the functional output of the mitochondrial genome, supporting a model in which mtDNA-encoded tRF contribute to phenotype modification.
2026-08-07 | GSE324681 | GEO
Project description:How mitochondrial DNA (mtDNA) polymorphisms influence complex phenotypes remains poorly understood. Using Mitochondrial-Nuclear eXchange (MNX) mice, we previously showed that mtDNA single nucleotide polymorphisms (SNP) modify metastasis, cardiovascular disease, and epigenetic marks independently of metabolic differences, suggesting a role for non-protein-coding loci. The only SNP correlating with these phenotypes resides in the gene encoding mitochondrial tRNA-Arginine (mt-tRNAArg (UCG), mt-TR). Here we identify and preliminarily characterize previously undescribed tRNA-derived fragments (tRF) generated from mt-TR. Northern blotting revealed distinct tRF that are differentially expressed between lung and liver and between sexes. Small RNA sequencing failed to capture these tRF unless samples were pre-treated to enzymatically remove non-canonical RNA termini and base methylation. Focusing on fragments with complete homology to mt-TR, the two most abundant tRF align uniquely to the mitochondrial genome and share conserved cleavage sites. Together, these findings uncover mitochondrial-derived tRF as a previously unrecognized small RNA metastasis modifiers and expand the functional output of the mitochondrial genome, supporting a model in which mtDNA-encoded tRF contribute to phenotype modification.
2026-08-07 | GSE324706 | GEO
Project description:tRNA-derived small RNA including tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs) plays significant roles in the various molecular mechanisms that underlie certain human diseases. of the generation of tRFs/tiRNAs and their potential roles during Dengue virus (DENV) infection is not yet known. Here, we have performed small RNA sequencing to identify the generation and alterations in tRF expression profiles of DENV infected Huh7 cells. Our results suggest that 733 tiRNAs/tRFs were found to be differentially expressed during DENV infection. Interestingly, 3’tRF population were found to be upregulated and i-tRF population were found to be downregulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to analyze the impact of differentially expressed tRFs on DENV pathogenesis. Our results suggest the significant involvement in transcriptional regulation via RNA polymerase II promoter and metabolic pathways. Overall, our study contributes significantly to our understanding of the roles played by tRFs in the complex dynamics of DENV infection.
2024-08-10 | GSE245081 | GEO
Project description:Here, we apply tRNA-seq and YAMAT-seq to profile the expressions of tRFs and tRNAs in plants. We provide a high-quality expression atlas of tRFs and tRNAs in Arabidopsis and rice, and uncover complex tRF population and the dynamic expressions of tRNA genes in plants.
2021-01-01 | GSE154165 | GEO
Project description:tRNA related fragments(tRF) and tRNA halves(tiRNA) are novel class of short non-coding RNA derived from tRNAs. Using RNA sequencing, we evaluated the tRFs/tiRNAs expression profiles in relapsed/refractory multiple myeloma and multiple myeloma patients. Bioinformatics analyses indicated that tRFs/tiRNAs may be involved in the progression and drug-resistance of multiple myeloma.
2021-05-19 | GSE171003 | GEO
Project description:Background: As couples struggle with infertility and livestock producers wish to rapidly improve genetic merit in their herd, assisted reproductive technologies (ART) have become increasingly popular in human medicine as well as the livestock industry. Utilizing ART can cause an increased risk of congenital overgrowth syndromes, such as Large Offspring Syndrome (LOS) in ruminants. A dysregulation of transcripts has been observed in bovine fetuses with LOS, which is suggested to be a cause of the phenotype. Our recent study identified variations in tRNA expression in LOS individuals, leading us to hypothesize that variations in tRNA expression can influence the availability of their processed regulatory products, tRNA-derived fragments (tRFs). Due to their resemblance in size to microRNAs, studies suggest that tRFs target mRNA transcripts and regulate gene expression. Thus, we have sequenced small RNA isolated from skeletal muscle and liver of day 105 bovine fetuses to elucidate the mechanisms contributing to LOS. Moreover, we have utilized our previously generated tRNA sequencing data to analyze the contribution of tRNA availability to tRF abundance. Results: 22,289 and 7,737 unique tRFs were predicted in the liver and muscle tissue respectively. The greatest number of reads originated from 5′ tRFs in muscle and 5′ halves in liver. In addition, mitochondrial (MT) and nuclear derived tRF expression was tissue-specific with most MT-tRFs and nuclear tRFs derived from LysUUU and iMetCAU in muscle, and AsnGUU and GlyGCC in liver. Despite variation in tRF abundance within treatment groups, we identified differentially expressed (DE) tRFs across Control-AI, ART-Normal, and ART-LOS groups with the most DE tRFs between ART-Normal and ART-LOS groups. Many DE tRFs target transcripts enriched in pathways related to growth and development in the muscle and tumor development in the liver. Finally, we found positive correlation coefficients between tRNA availability and tRF expression in muscle (R = 0.47) and liver (0.6). Conclusion: Our results highlight the dysregulation of tRF expression and its regulatory roles in LOS. These tRFs were found to target both imprinted and non-imprinted genes in muscle as well as genes linked to tumor development in the liver. Furthermore, we found that tRNA transcription is a highly modulated event that plays a part in the biogenesis of tRFs. This study is the first to investigate the relationship between tRNA and tRF expression in combination with ART-induced LOS.
2022-11-15 | GSE213525 | GEO
Project description: Not available
| S-EPMC6049499 | biostudies-literature
Project description:Transfer RNA-derived fragments (tRFs) are a class of small non-coding RNAs that have exhibited several functions in cancer. Recent studies have shown that mutations in tRNA genes can lead to global changes in tRF expression levels and may affect tRF function, highlighting the need to further elucidate the regulation and functions of tRFs in cancer. Here, we conducted a pan-cancer analysis of tRF quantitative trait loci (tRFQTLs), encompassing 16,703 genetic variants associated with tRF expression across 31 cancer types. A joint analysis of GWAS data revealed that tRFQTLs were preferentially enriched in cancer risk loci and colocalized with 106 GWAS variants, explaining a substantial portion of cancer heritability. Moreover, tRFs regulated by tRFQTLs were enriched in cancer-related pathways and correlated with drug response and immune infiltration. Notably, polygenic risk score models incorporating tRFQTLs improved high-risk population identification. Investigation of large-scale population cohorts revealed a tRFQTL, rs9461276, associated with colorectal cancer (CRC) risk. In biological assays, the rs9461276-C allele increased tRF-18-HSQS52D2 expression, which suppressed CRC malignant phenotypes. Mechanistically, tRF-18-HSQS52D2 bound to the 3'UTR of POU2F1, destabilizing the oncogenic transcript. Integrated RNA sequencing and ChIP-seq assays indicated that POU2F1 enhanced CRC cell proliferation by activating various pathological pathways associated with oxidative and glycolytic metabolism, mitotic stability, and cell cycle regulation. Finally, a database (Cancer-tRFQTL) was generated as a resource to support investigation into tRF-mediated mechanisms and genetic basis of tRF expression in human cancers. Overall, this study helps advance the understanding of tRFs in cancer pathogenesis.
2025-08-05 | GSE304444 | GEO
Project description:Protozoan parasites of the genus Leishmania, the causative agents of human leishmaniasis, have evolved mechanisms to manipulate host cell functions to their advantage. Recently, small non-coding RNAs have been identified as contributors to the pathogenesis of Leishmania infection. An increasing number of studies have demonstrated that Leishmania tRNA-derived small non-coding RNAs, also known as Leishmania tRNA-derived fragments (Ld-tRFs), can be delivered to host cells via exosomes, thereby influencing host cell function. Here, we investigated the potential effects of Leishmania exosomal Ld-tRF-Asp and Ld-tRF-Leu in host macrophages. SILAC (Stable Isotope Labelling by Amino acids in Cell culture) based quantitative proteomics was used to investigate the effects of synthetic Ld-tRF-Asp and Ld-tRF-Leu by analyzing how these Ld-tRFs affect the macrophage proteome. Ld-tRF-Asp modulated 20 proteins, whereas Ld-tRF-Leu affected 18 proteins in macrophages. Interestingly, 7 of the Ld-tRF-Asp-modulated proteins and 6 of the Ld-tRF-Leu-modulated proteins showed potential pro-leishmania effects. Biochemical isolation of Argonaute (Ago) protein complexes by “Ago proteins Affinity Purification by Peptide,” followed by identification of interacting small non-coding RNAs, revealed the selective presence of both tRFs in Leishmania-infected macrophages. This striking finding suggested that Ld-tRFs engage macrophage Agos for their effects. In addition, an in vivo biotin-RNA pull-down assay showed that Ld-tRF-Leu selectively interacted with Ago 1, suggesting that Ago 1 is the preferred Ago guiding Ld-tRFs to target host genes. Taken together, this study shows, for the first time, that Leishmania exosomal tRFs significantly alter the host macrophage proteome in favour of Leishmania survival. This may offer new insights into the mechanisms of leishmaniasis and may provide future therapeutic interventions targeting these regulatory molecules.
2026-09-14 | PXD072695 | Pride
Project description:Parental dietary conditions can influence the metabolic traits of offspring. In mice, paternal consumption of low protein diet alters cholesterol and lipid metabolism of progeny. Here, we examine RNA species expressed in male reproductive tissues of mice. Protein restriction leads to altered levels of multiple small RNAs in mature sperm, as well as throughout the male reproductive tract, with decreased levels of let-7 family members and increased levels of 5â?? fragments of tRNA-Gly isoacceptors. Intriguingly, tRNA fragments are scarce in the testis, but their levels increase in sperm during posttesticular maturation in the epididymis. We find that epididymosomes â?? extracellular vesicles which fuse with sperm during epididymal transit â?? exhibit RNA payloads closely matching those of mature sperm, and can deliver tRNA fragments to immature sperm in vitro both in mouse and in bull. Finally, we show that tRNA-Gly-GCC fragments play a role in repressing genes associated with the endogenous retroelement MERVL, both in ES cells and in preimplantation embryos. Our results shed light on small RNA biogenesis during post-testicular sperm maturation, and link tRNA fragments to regulation of endogenous retroelements active in the early embryo. E14 mESCs were transfected with LNA-containing oligos antisense to tRF-GG or GFP-esiRNA as control, then either total RNA was isolated or 80S ribosomes were isolated from Rnase-digested whole cell lysate, and footprints between 26-32nt were collected for ribosome profiling library construction using a kit-free protocol based on Heyer et al. 2015 NAR.
2016-01-04 | E-GEOD-74537 | biostudies-arrayexpress