TRF-seq landscapes the variation of tRNA derived fragments after mouse liver injury
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE144698 | GEO | 2021/06/05
REPOSITORIES: GEO
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Project description:Transfer RNA-derived fragments (tRFs) and transfer RNA halves (tiRNAs) have been shown to play crucial roles in gene regulation. This study targets to reveal the expression profile of tRFs and tiRNAs and their possible biological roles in lung adenocarcinoma (LUAD). Five paired clinical lung adenocarcinoma tissues (LAT) and adjacent normal lung tissues (ANLT) were selected to conduct the expression of tRFs and tiRNAs. The sequencing results showed that 109 tRFs and tiRNAs were differentially expressed between LAT and ANLT, out of which 60 were upregulated and 49 were downregulated. Compared with ANLT, lower expression levels of three tRF-1s (tRF-Ser-TGA-010, tRF-Arg-CCT-018 and tRF-Val-CAC-017) in LAT were verified by quantitative real-time polymerase chain reaction. Subsequently, the putative target genes of tRF-1s were analyzed by computational prediction and the top ten significant results of GO and KEGG pathway enrichment analysis were presented. These signaling pathways are involved in the carcinogenesis of LUAD. This study has showed a landscape of tRFs and tiRNAs expression profiles in LUAD. Three newly found differentially expressed down-regulated tRF-1s may be involved in the pathogenesis of LUAD and might serve as potential diagnostic biomarkers.
2022-01-19 | GSE165918 | 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:tRF-seq landscapes the variation of tRNA derived fragments after mouse liver injury
| PRJNA604603 | ENA
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-derived fragments (tRFs) play critical roles in cellular process, and we have previously reported that tRFs is involved in ischemia reperfusion injury induced acute kidney injury (IRI-AKI). However, the precise involvement of tRFs in IRI-AKI remains obscure. This study aims to elucidate the impact of tRF-Val-TAC-004 (tRF-Val) on IRI-AKI and to uncover the underlying mechanisms. Our observations reveal a significant downregulation of tRF-Val in the kidneys of ischemic mice. Overexpression of tRF-Val mitigated renal dysfunction, morphological damage, and tubular cells apoptosis in IRI-AKI mice, while its inhibition exacerbated these effects. Similar outcomes were replicated in CoCl2-treated BUMPT cells upon transfection with tRF-Val mimic or inhibitor. Mechanistically, dual-luciferase reporter assays and AGO-RIP qPCR analyses demonstrated that tRF-Val suppresses Apaf1 expression by targeting the 3’-UTR of Apaf1 mRNA through AGO-dependent sequence complementarity. Furthermore, the protective efficacy of tRF-Val was notably weakened when Apaf1-overexpressing plasmids were transfected into CoCl2-treated BUMPT cells. In summary, these novel findings unveil the protective role of tRF-Val against IRI-AKI through inhibition of Apaf1-mediated apoptosis.
2024-12-18 | GSE282997 | GEO
Project description:tRNA fragments (tRFs) are small non-coding RNA molecules that are generated through the cleavage of tRNAs and have been implicated in various biological processes. Among the different types of tRFs, the 3′-tRFs have attracted considerable scientific interest due to their regulatory role in gene expression. In this study, we investigated the role of 3′-tRF-CysGCA, a tRF derived from cleavage in the T-loop of tRNACysGCA, in the regulation of gene expression in HEK-293 cells. Previous studies have shown that 3′-tRF-CysGCA is incorporated into the RISC complex and interacts with Argonaute proteins, suggesting its involvement in the regulation of gene expression. However, the general role and effect of the deregulation of 3′-tRF-CysGCA levels in human cells have not been investigated so far. To address this gap, we stably overexpressed 3′-tRF-CysGCA in HEK-293 cells and performed transcriptomics and proteomics experiments. Moreover, we validated the interaction of this tRF with putative targets whose levels were affected after 3′-tRF-CysGCA overexpression. Last, we investigated the implication of 3′-tRF-CysGCA in various pathways using extensive bioinformatics analysis. Our results indicate that 3′-tRF-CysGCA overexpression led to changes in the cell expression profile, and we identified multiple pathways that were affected by the deregulation of this tRF. Additionally, our reporter assays demonstrated that 3′-tRF-CysGCA directly interacted with TMPO and ERGIC1, leading to changes in their expression levels. Taken together, these findings suggest that 3′-tRF-CysGCA plays a significant role in the regulation of gene expression and highlight the potential importance of this tRF in cellular processes.
2023-11-30 | PXD044218 | Pride
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:MicroRNAs (miRNAs) are a well-characterized class of small RNAs (sRNAs) that regulate gene expression post-transcriptionally. miRNAs function within a complex milieu of other sRNAs of similar size and abundance, with the best characterized being tRNA fragments or tRFs. The mechanism by which the RNA-induced silencing complex (RISC) selects for specific sRNAs over others is not entirely understood in human cells. Several highly expressed tRNA trailers (tRF-1s) are strikingly similar to microRNAs in length but are generally excluded from the microRNA effector pathway. This exclusion provides a paradigm for identifying mechanisms of RISC selectivity. Here, we show that 5' to 3' exoribonuclease XRN2 contributes to human RISC selectivity. Although highly abundant, tRF-1s are highly unstable and degraded by XRN2 which blocks tRF-1 accumulation in RISC. We also find that XRN mediated degradation of tRF-1s and subsequent exclusion from RISC is conserved in plants. Our findings reveal a conserved mechanism that prevents aberrant entry of a class of highly produced sRNAs into Ago2.
2023-04-24 | GSE184124 | GEO
Project description:Pseudouridylation (Ψ) is the most abundant and widespread type of RNA epigenetic modification in living organisms; however, the biological role of Ψ remains poorly understood. Here, we show that a Ψ-driven posttranscriptional program steers translation control to impact stem cell commitment during early embryogenesis. Mechanistically, the Ψ ‘writer’ PUS7 modifies and activates a network of tRNA-derived fragments (tRFs) targeting the translation initiation complex. PUS7 inactivation in embryonic stem cells impairs tRF-mediated translational regulation leading to increased protein biosynthesis and abnormal germ layer specification. Remarkably, dysregulation of PUS7 and tRFs in myeloid malignancies associates with altered translation rates, suggesting a role of Ψ in leukemogenesis. Our findings unveil a critical function of Ψ in directing translational control in stem cells with important implications for human disease.
2018-04-11 | PXD008676 | Pride