Dataset Information

Alteration of mRNA 5-Methylcytosine Modification in Neurons After OGD/R and Potential Roles in Cell Stress Response and Apoptosis.

ABSTRACT: Epigenetic modifications play an important role in central nervous system disorders. As a widespread posttranscriptional RNA modification, the role of the m⁵C modification in cerebral ischemia-reperfusion injury (IRI) remains poorly defined. Here, we successfully constructed a neuronal oxygen-glucose deprivation/reoxygenation (OGD/R) model and obtained an overview of the transcriptome-wide m⁵C profiles using RNA-BS-seq. We discovered that the distribution of neuronal m⁵C modifications was highly conserved, significantly enriched in CG-rich regions and concentrated in the mRNA translation initiation regions. After OGD/R, modification level of m⁵C increased, whereas the number of methylated mRNA genes decreased. The amount of overlap of m⁵C sites with the binding sites of most RNA-binding proteins increased significantly, except for that of the RBM3-binding protein. Moreover, hypermethylated genes in neurons were significantly enriched in pathological processes, and the hub hypermethylated genes RPL8 and RPS9 identified by the protein-protein interaction network were significantly related to cerebral injury. Furthermore, the upregulated transcripts with hypermethylated modification were enriched in the processes involved in response to stress and regulation of apoptosis, and these processes were not identified in hypomethylated transcripts. In final, we verified that OGD/R induced neuronal apoptosis in vitro using TUNEL and western blot assays. Our study identified novel m⁵C mRNAs associated with ischemia-reperfusion in neurons, providing valuable perspectives for future studies on the role of the RNA methylation in cerebral IRI.

SUBMITTER: Jian H

PROVIDER: S-EPMC7887326 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Alteration of mRNA 5-Methylcytosine Modification in Neurons After OGD/R and Potential Roles in Cell Stress Response and Apoptosis.

Jian Huan H Zhang Chi C Qi ZhangYang Z Li Xueying X Lou Yongfu Y Kang Yi Y Deng Weimin W Lv Yigang Y Wang Chaoyu C Wang Wei W Shang Shenghui S Hou Mengfan M Zhou Hengxing H Feng Shiqing S

Frontiers in genetics 20210203

Epigenetic modifications play an important role in central nervous system disorders. As a widespread posttranscriptional RNA modification, the role of the m5C modification in cerebral ischemia-reperfusion injury (IRI) remains poorly defined. Here, we successfully constructed a neuronal oxygen-glucose deprivation/reoxygenation (OGD/R) model and obtained an overview of the transcriptome-wide m5C profiles using RNA-BS-seq. We discovered that the distribution of neuronal m ...[more]

PMID: 33613646

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Project description:Neuronal apoptosis is a major pathological hallmark of the neonatal hypoxic-ischemic brain damage (HIBD); however, the role of miR-7a-2-3p in the regulation of HIBD remains unknown. The purpose of this study was to explore the possible roles of miR-7a-2-3p in brain injury using a hypoxia-ischemia model in rats and oxygen-glucose deprivation (OGD) model in vitro. Firstly, we established the hypoxia-ischemia (HI) model and verified the model using Zea Longa scores and MRI in rats. Next, the changes of miR-7a-2-3p were screened in the ischemic cortex of neonatal rats by qRT-PCR at 12, 48, and 96 h after HIBD. We have found that the expression of miR-7a-2-3p in the HI rats decreased significantly, compared with the sham group (P < 0.01). Then, we established the OGD model in PC12 cells, SH-SY5Y cells and primary cortical neurons in vitro and qRT-PCR was used to confirm the changes of miR-7a-2-3p in these cells after the OGD. In order to determine the function of miR-7a-2-3p, PC12 cells, SH-SY5Y cells and rat primary cortical neurons were randomly divided into normal, OGD, mimic negative control (mimic-NC) and miR-7a-2-3p groups. Then, Tuj1+ (neuronal marker) staining, TUNEL assay (to detect apoptotic cells) and MTT assay (to investigate cell viability) were performed. We have found that the number of PC12 cells, SH-SY5Y cells and cortical neurons in the miR-7a-2-3p groups increased significantly (P < 0.01) in comparison to the OGD groups. The survival of cortical neurons in the miR-7a-2-3p group was improved markedly (P < 0.01), while the apoptosis of neurons in the miR-7a-2-3p group was significantly decreased (P < 0.01), compared with the normal group. Lastly, we investigated the target genes of miR-7a-2-3p by using the prediction databases (miRDB, TargetScan, miRWalk, and miRmap) and verified the target genes with qRT-PCR in the HI rats. Bioinformatics prediction showed that Vimentin (VIM), pleiomorphic adenoma gene 1(PLAG1), dual specificity phosphatase 10 (DUSP10), NAD(P)H dehydrogenase, quinone 1 (NQO1) and tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) might be the targets of miR-7a-2-3p and the qRT-PCR confirmed that VIM increased in the HI rats (P < 0.01). In conclusion, miR-7a-2-3p plays a crucial role in the hypoxic-ischemic injury, and is associated with regulation of VIM.

Project description:BackgroundIn plants, histone modification (HM) genes participate in various developmental and defense processes. Gramineae plants (e.g., Triticum aestivum, Hordeum vulgare, Sorghum bicolor, Setaria italica, Setaria viridis, and Zea mays) are important crop species worldwide. However, little information on HM genes is in Gramineae species.ResultsHere, we identified 245 TaHMs, 72 HvHMs, 84 SbHMs, 93 SvHMs, 90 SiHMs, and 90 ZmHMs in the above six Gramineae species, respectively. Detailed information on their chromosome locations, conserved domains, phylogenetic trees, synteny, promoter elements, and gene structures were determined. Among the HMs, most motifs were conserved, but several unique motifs were also identified. Our results also suggested that gene and genome duplications potentially impacted the evolution and expansion of HMs in wheat. The number of orthologous gene pairs between rice (Oryza sativa) and each Gramineae species was much greater than that between Arabidopsis and each Gramineae species, indicating that the dicotyledons shared common ancestors. Moreover, all identified HM gene pairs likely underwent purifying selection based on to their non-synonymous (Ka)/synonymous (Ks) nucleotide substitutions. Using published transcriptome data, changes in TaHM gene expression in developing wheat grains treated with brassinosteroid, brassinazole, or activated charcoal were investigated. In addition, the transcription models of ZmHMs in developing maize seeds and after gibberellin treatment were also identified. We also examined plant stress responses and found that heat, drought, salt, insect feeding, nitrogen, and cadmium stress influenced many TaHMs, and drought altered the expression of several ZmHMs. Thus, these findings indicate their important functions in plant growth and stress adaptations.ConclusionsBased on a comprehensive analysis of Gramineae HMs, we found that TaHMs play potential roles in grain development, brassinosteroid- and brassinazole-mediated root growth, activated charcoal-mediated root and leaf growth, and biotic and abiotic adaptations. Furthermore, ZmHMs likely participate in seed development, gibberellin-mediated leaf growth, and drought adaptation.

Dataset Information

Alteration of mRNA 5-Methylcytosine Modification in Neurons After OGD/R and Potential Roles in Cell Stress Response and Apoptosis.

Publications

Alteration of mRNA 5-Methylcytosine Modification in Neurons After OGD/R and Potential Roles in Cell Stress Response and Apoptosis.

Similar Datasets

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