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TRF-Val-TAC-004 protects against renal ischemia-reperfusion injury via attenuating Apaf1-mediated apoptosis

ABSTRACT: tRNA-derived fragments (tRFs) play critical roles in cellular process, and we have previously reported that tRFs are 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 uncover the underlying mechanisms. Our observations reveal a significant downregulation of tRF-Val in IRI-AKI mice and its overexpression mitigated renal dysfunction, morphological damage, and 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 assay and AGO-RIP qPCR analyses demonstrated that tRF-Val suppresses Apaf1 expression by targeting the 3’-UTR of Apaf1 mRNA. Furthermore, the protective efficacy of tRF-Val was notably weakened by Apaf1-overexpressing plasmids. In summary, these novel findings unveil the protective role of tRF-Val against IRI-AKI through inhibition of Apaf1-mediated apoptosis.

ORGANISM(S): Mus musculus

PROVIDER: GSE282997 | GEO | 2024/12/18

REPOSITORIES: GEO

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tRF-Val-TAC-004 protects against renal ischemia-reperfusion injury via attenuating Apaf1-mediated apoptosis

Project description:tRF-Val-TAC-004 protects against renal ischemia-reperfusion injury via attenuating Apaf1-mediated apoptosis

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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

tRF&tiRNA sequencing of human PTC tissues and corresponding paracancer tissues

Project description:Purpose: To study the expression and potential significance of tRF and tiRNA in PTC (Papillary thyroid carcinoma) by sequencing tRF and tiRNA in PTC tissues and corresponding paracancer tissues of thyroid cancer patients. Methods: Four pairs of PTC tissues and paracancer tissues were collected. Small RNA sequencing was performed on Illumina NexSeq instrument. Results: If P ≤ 0.05, fold change > 1.5 as the cutoff, there were 27 up-regulated tRFs & tiRNAs and 20 down-regulated tRFs & tiRNAs. Conclusions: Among the differentially expressed tRFs & tiRNAs, tiRNA-1:34-Lys-CTT-2 and tRF-1:30-Gly-CCC-3 may be the potential novel regulatory factors.

2022-02-26 | GSE197438 | GEO

tRF and tiRNA profiles in lung adenocarcinoma.

Project description:We investigate tRF and tiRNA profiles in lung adenocarcinoma and adjacent tissues using a NextSeq system. Total RNA was extracted from tissues and pretreated to remove the RNA modifications. In patients with lung adenocarcinoma, 338 types of tRFs and tiRNAs were detected via sequencing, 284 of which were not previously reported. Compared with the adjacent tissues, 17 types of tRFs and tiRNAs comprising 34 subtypes were found to be abnormally expressed in lung adenocarcinoma tissues, 20 of which were upregulated and 14 of which were downregulated. Finally, we show that tRF and tiRNA profiles in lung adenocarcinoma and adjacent tissues and identify several dysregulated tRFs and tiRNAs.

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tRF-seq landscapes the variation of tRNA derived fragments after mouse liver injury

Project description:In order to intensively elucidate the metabolic characteristics of tRFs after liver injury, we performed tRF-seq by high throughput sequencing. We found that after liver injury, large abundance of tRFs were produced. Especially, the tRF-1s largely vary during the liver injury process and may play important role in the liver disease.

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tRF & tiRNA sequencing of breast cancer tissue samples and matched non-tumor adjacent tissues

Project description:Purposes: To investigate the biological function of tRF in breast cancer by tRF and tiRNA sequencing Methods: Breast cancer tissue samples and matched non-tumor adjacent tissues were obtained from five patients. Small RNA sequencing was performed on Illumina NexSeq instrument Results: If P ≤ 0.05, fold change ≥ 2 as the cut off, there were 3 up-regulated tRFs & tiRNAs and 13 down-regulated tRFs & tiRNAs. Conclusions:There were 3 up-regulated tRFs & tiRNAs and 13 down-regulated tRFs & tiRNAs in breast cancer tissue samples and matching adjacent tissue samples

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YBX1-dependent LNA-tRF-mediated modulation of gene expression

Project description:In order to identify YBX1-dependent targets that are modulated upon changing the levels of endogenous tRFs, we used transient transfection of antisense locked-nucleic acids (LNAs) against tRFAsp, tRFGly, tRFGlu, and tRFTyr followed by microarray profiling. Synthetic antisense locked-nucleic acids (LNAs) targeting the YBX1 binding site on tRFAsp, tRFGly, tRFGlu, and tRFTyr were transfected into control and YBX1-knockdown cells to identify YBX1-dependent targets that are modulated due to tRF loss-of-function.

2015-05-08 | E-GEOD-63564 | biostudies-arrayexpress

A Pilot Study for Protective Roles of tRNA-Derived Small RNA tRF-Ile-AAT-019 in Pathological Progression of Psoriasis

Project description:Psoriasis is a chronic recurrent inflammatory skin disease that is characterized by abnormal proliferation and differentiation of keratinocytes (KCs), angiogenesis and skin inflammation. tRNA-derived small RNA (tsRNA), including tRNA halves and tRNA fragments (tRFs), is a novel class of short non-coding RNA, possessing regulatory functions in many diseases. However, its role in the pathological development of psoriasis has been unknown. In this pilot study, we conducted small RNA sequencing to screen differentially expressed tRFs in psoriatic skin lesions as compared with normal controls. We found 130 upregulated and 104 downregulated tRFs, among which downregulation of tRF-Ile-AAT-019 in psoriatic skin lesions was further confirmed. Bioinformatics analysis by TargetScan and Miranda algorithms revealed that tRF-Ile-AAT-019 might target SERPINE1, thus regulating HIF-1α signaling pathway. We next showed that increased tRF-Ile-AAT-019 could downregulate expressions of SERPINE1, HIF-1α and vascular proliferative markers such as CD34, CD31, Factor VIII, and VEGF, but upregulate expressions of KCs differentiation markers including Keratin1 and Involucrin. Our data suggest that tRF-Ile-AAT-019 plays a protective role in the pathological progression of psoriasis via targeting SERPINE1 and blocking HIF-1α signaling pathway, leading to control KCs differentiation and vascular proliferation. This data provides a potential novel targeting pathway for the disease treatment.

2021-02-19 | GSE167057 | GEO

tRNA-Derived Fragments Expression Profile and Their Potential Roles in Lung Adenocarcinoma Tissues

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

tRF & tiRNA sequencing of intestinal biopsies from IBS-D patients

Project description:Purposes: To investigate the epigenetic mechanism of IBS-D(Irritable Bowel Syndrome with Diarrhea) by tRF & tiRNA sequencing in intestinal biopsies of IBS-D patients and healthy volunteers Methods: Five IBS-D and five healthy volunteers were screened, and biopsies were taken under colonoscopy. Small RNA sequencing was performed on Illumina NexSeq instrument Results:If P < 0.05, fold change > 1.5 as the cutoff, there were 14 up-regulated tRFs & tiRNAs and 14 down-regulated tRFs & tiRNAs. Conclusions:There were 14 up-regulated tRFs & tiRNAs and 14 down-regulated tRFs & tiRNAs in intestinal tissues of IBS-D .

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