Identification of tRNA-derived Small RNAs and Their Potential Roles in Myocardial Infarction
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE249120 | GEO | 2025/04/30
REPOSITORIES: GEO
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Project description:We report the application of high-throughput RNA sequencing technology to examine expression profiling of transfer RNA (tRNA)-derived small RNAs (tsRNAs) in a normal control group (Norm group), isoproterenol (ISO)-induced myocardial ischemic group (MI group), and CR-pretreatment plus ISO-induced myocardial ischemic group (CR+MI group). A total of 714 precisely matched tsRNAs were identified in the myocardial tissues from the three groups of rats (701 in Norm, 708 in MI, and 712 in CR+MI). We find that 302 tsRNAs were identified to be notably dysregulated in the MI group: 166 tsRNAs were upregulated while 136 tsRNAs were downregulated compared with those in the Norm group. After CR pretreatment, we identified 136 tsRNAs that were significantly altered compared with those in the MI group: 45 were upregulated while 91 were downregulated. This study provides new ideas for future research on elucidating the mechanisms of CR pretreatment through regulating tsRNAs levels in myocardial ischemic injury.
2020-10-01 | GSE158781 | GEO
Project description:Specific environmental insults cause the limited fragmentation of transfer RNAs (tRNAs) into tRNA-derived small RNAs (tsRNAs), which have been implicated in a wide range of biological processes. tRNA fragmentation results from endonucleolytic activities targeting single-stranded tRNA regions. However, how a tRNA with a single hydrolyzed phosphodiester bond in the anticodon loop (‘nicked’ tRNA) gives rise to distinct tsRNAs remains poorly understood. By utilizing biochemical fractionation of tsRNA-containing ribonucleoprotein complexes (RNPs) coupled with LC-MS/MS, we identified several RNA helicase enzymes that represent putative tRNA/tsRNA processing enzymes. Furthermore, a combination of biochemical and computational approaches revealed that specific RNA helicases indeed bind specific tRNAs with high affinity, as well as process nicked tRNAs into individual tsRNAs. In summary, these findings reveal that tRNA-derived duplexes can be substrates of well-known RNA helicases, thereby expanding their potential for cellular function to the creation of individual tsRNAs during the cellular stress response.
2023-01-09 | PXD029869 | Pride
Project description:Apart from their primordial role in protein synthesis, tRNAs can be cleaved to produce tRNA-derived small RNAs (tsRNAs). The biological functions of tsRNAs in plants remain largely unknown. In this study, we developed RtcB-based RNA sequencing, a method that captures and distinguishes between 2’,3’-cyclic-phosphate (cP)-terminated RNAs and 3’-OH-terminated RNAs, and profiled 5’ tsRNAs and 5’ tRNA halves in Arabidopsis thaliana. We found that Arabidopsis 5’ tsRNAs and 5’ tRNA halves predominantly contain a cP at the 3’ end and require S-like RNase 1 (RNS1) and RNS3 for their production. One of the most abundant 5’ tsRNA, 5’ tsR-Ala, likely by associating with AGO1, negatively regulates Cytochrome P450 71A13 (CYP71A13) expression and camalexin biosynthesis to repress anti-fungal defense. 5’ tsR-Ala is downregulated upon fungal infection. Our study provides a global view of 5’ tsRNAs and 5’ tRNA halves in Arabidopsis and unravels an important role of a 5’ tsRNA in regulating anti-fungal defense.
2022-02-16 | GSE183560 | GEO
Project description:Background: It has been reported that sacubitril/valsartan can improve cardiac function in acute myocardial infarction (AMI) patients complicated by heart failure (HF). However, a number of patients cannot be treated successfully; this phenomenon is called sacubitril/valsartan resistance (SVR), and the mechanisms remain unclear. Methods:In our present research, the expression profiles of tRNA-derived small RNAs (tsRNAs) in SVR along with NSVR patients were determined by RNA sequencing. Through bioinformatics, qRT–PCR, and cell-based experiments, we identified SVR-related tsRNAs and confirmed their diagnostic value, predicted their targeted genes, and explored the enriched signal pathways as well as regulatory roles of tsRNAs in SVR. Results:Our research indicated that 36 tsRNAs were upregulated and that 21 tsRNAs were downregulated in SVR. Among these tsRNAs, the expression of tRF-59:76-Tyr-GTA-2-M3 and tRF-60:76-Val-AAC-1-M5 was upregulated, while the expression of tRF-1:29-Gly-GCC-1 was downregulated in the group of SVR. Receiver operating characteristic (ROC) curve analysis demonstrated that these three tsRNAs were potential biomarkers of the therapeutic heterogeneity of sacubitril/valsartan. Moreover, tRF-60:76-Val-AAC-1-M5 might target Tnfrsf10b and Bcl2l1 to influence the observed therapeutic heterogeneity through the lipid and atherosclerosis signaling pathways. Conclusions:Hence, tsRNA might play a vital role in SVR. These discoveries provide new insights for the mechanistic investigation of responsiveness to sacubitril/valsartan.
2022-10-19 | GSE207882 | GEO
Project description:During stress conditions, particular tRNAs are cleaved by stress-induced endonucleases resulting in distinct tRNA-derived small RNAs (tsRNAs). These small RNAs have been implicated in a wide array of mostly stress-related biological processes, however how exactly they exert their functions mechanistically is still largely unknown. Since parental tRNAs carry post-transcriptional modifications, stress-induced tsRNAs are likely modified, too. In order to use endogenously modified tsRNAs, we developed a biochemical pipeline for the production and purification of specific tsRNAs using a human cell culture system. Ectopic expression of Angiogenin combined with chromatography of small RNAs resulted in the production of endogenously modified 5’ tsRNAs on a preparative scale. Small RNA sequencing on purified tsRNAs was used to determine the identity and purity of the 5’ tsRNA preparations.
2020-03-01 | GSE139124 | GEO
Project description:Transfer RNA (tRNA) molecules contain a variety of post-transcriptional modifications which are crucial for tRNA stability, translation efficiency, and fidelity. Besides their canonical roles in translation, tRNAs also originate tRNA-derived small RNAs (tsRNAs), a class of small non-coding RNAs with regulatory functions ranging from translation regulation, to gene expression control and cellular stress response. Recent evidence show that tsRNAs are also modified, however the impact of tRNA epitranscriptome deregulation on tsRNAs generation is only now beginning to be uncovered. The 5-methyluridine (m5U) modification at position 54 of cytosolic tRNAs is one of the most common and conserved tRNA modifications among species. This modification is catalyzed by the tRNA methyltransferase TRMT2A, but its biological role remains largely unexplored. Here, we show that TRMT2A knockdown in human cells induces m5U54 tRNA hypomodification, resulting in angiogenin (ANG) dependent tsRNA formation. More specifically, m5U54 hypomodification is followed by ANG overexpression and tRNA cleavage near the anticodon, resulting in accumulation of 5’tRNA-derived stress-induced RNAs (5’tiRNAs), in particular 5’tiRNA-GlyGCC and 5’tiRNA-GluCTC. Additionally, transcriptomic analysis confirms that down-regulation of TRMT2A and consequently m5U54 hypomodification impacts the cellular stress response and RNA stability, which is often correlated with tsRNA generation. Accordingly, exposure to oxidative stress conditions induces TRMT2A down-regulation and tsRNA formation in mammalian cells. These results establish a link between tRNA demethylation and tsRNAs formation and unravel m5U54 as a tRNA cleavage protective mark.
2021-04-20 | GSE164405 | GEO
Project description:Transfer RNA (tRNA) molecules contain a variety of post-transcriptional modifications which are crucial for tRNA stability, translation efficiency, and fidelity. Besides their canonical roles in translation, tRNAs also originate tRNA-derived small RNAs (tsRNAs), a class of small non-coding RNAs with regulatory functions ranging from translation regulation, to gene expression control and cellular stress response. Recent evidence show that tsRNAs are also modified, however the impact of tRNA epitranscriptome deregulation on tsRNAs generation is only now beginning to be uncovered. The 5-methyluridine (m5U) modification at position 54 of cytosolic tRNAs is one of the most common and conserved tRNA modifications among species. This modification is catalyzed by the tRNA methyltransferase TRMT2A, but its biological role remains largely unexplored. Here, we show that TRMT2A knockdown in human cells induces m5U54 tRNA hypomodification, resulting in angiogenin (ANG) dependent tsRNA formation. More specifically, m5U54 hypomodification is followed by ANG overexpression and tRNA cleavage near the anticodon, resulting in accumulation of 5’tRNA-derived stress-induced RNAs (5’tiRNAs), in particular 5’tiRNA-GlyGCC and 5’tiRNA-GluCTC. Additionally, transcriptomic analysis confirms that down-regulation of TRMT2A and consequently m5U54 hypomodification impacts the cellular stress response and RNA stability, which is often correlated with tsRNA generation. Accordingly, exposure to oxidative stress conditions induces TRMT2A down-regulation and tsRNA formation in mammalian cells. These results establish a link between tRNA demethylation and tsRNAs formation and unravel m5U54 as a tRNA cleavage protective mark.
2021-04-20 | GSE164168 | GEO
Project description:The progression of myocardial infarction (MI) involves multiple metabolic disorders. Bile acid metabolites have been increasingly recognized as pleiotropic signalling molecules that regulate multiple cardiovascular functions. G protein-coupled bile acid receptor (TGR5) is one of the receptors sensing bile acids to mediate their biological functions. In this study, we aimed to elucidate the effects of bile acids-TGR5 signaling pathways in myocardial infarction (MI).Mice underwent either the LAD ligation model of MI or sham operation. Both MI and sham mice were gavaged with 10 mg/kg/d DCA or vehicle control since 3-day before the operation. Administration of DCA improved cardiac function at the 3th-day post-MI. The effects of DCA in the heart were determined by RNA-sequencing experiments.
2020-09-24 | GSE158415 | GEO
Project description:The use of cDNA microarrays has made it possible to analyze expression of thousands of genes simultaneously. We employed microarray gene expression profiling of porcine cDNA to compare myocardial gene expression in infarct core and remote myocardium at 1 week (n=3), 4 weeks (n=3), and 6 weeks (n=3) after surgically induced myocardial infarction (MI) and in sham-operated controls (n=3). More than 8,000 cDNA sequences were identified in myocardium that showed differential expression in response to MI. Different temporal and spatial patterns of gene expression were recognized in the infarct core tissue within this large set of data. Microarray gene profiling revealed candidate genes, some of them described for the first time, which elucidate changes in biological processes at different stages after MI. We evaluated temporal gene expression in a porcine model of myocardial infarction by microarray technology. Nine female pigs (Sus scrofa crossbreed Landrace x Large White) weighing 30-40 kg were subjected to experimental MI by a double-ligation of the first marginal branch of the circumflex artery. Animals were randomly sacrificed at 1 week (n=3), 4 weeks (n=3), or 6 weeks (n=3) after MI. Three paired myocardial samples from the infarct core and remote myocardium were analyzed at each time point. Myocardial samples from sham-operated animals (open-chest cardiac exposure without coronary artery ligation; n=3) were included as physiological controls.
2013-03-01 | E-GEOD-34569 | biostudies-arrayexpress
Project description:Thyroid hormone improves left ventricular remodeling and cardiac performance after myocardial infarction (MI), but the molecular basis is unknown. This study was designed to detect gene expression changes in left ventricular non-infarcted areas at 4 weeks following myocardial infarction with and without thyroid hormone treatment. The results suggest that altered expression of genes for molecular function and biological process may be involved in the beneficial effects of thyroid hormone treatment following myocardial infarction in rats. MI was produced by ligation of the left anterior descending coronary artery in female SD rats. Rats were divided into the following groups: (1) Sham MI, (2) MI, and (3) MI+T4 treatment (T4 pellet 3.3mg, 60 days release, implanted subcutaneously immediately following MI). Four weeks after surgery, total RNA was isolated from left ventricular non-infarcted areas for microarray analysis using the Illumina RatRef-12 Expression BeadChip Platform.
2012-04-30 | E-GEOD-35088 | biostudies-arrayexpress