Alteration of mRNA 5-Methylcytosine Modification in Neurons After OGD/R and Potential Roles in Cell Stress Response and Apoptosis
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-glucos...
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2021.633681/full |
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| author | Huan Jian Huan Jian Chi Zhang Chi Zhang ZhangYang Qi ZhangYang Qi Xueying Li Xueying Li Xueying Li Yongfu Lou Yongfu Lou Yi Kang Yi Kang Weimin Deng Yigang Lv Yigang Lv Chaoyu Wang Chaoyu Wang Wei Wang Wei Wang Shenghui Shang Shenghui Shang Mengfan Hou Mengfan Hou Hengxing Zhou Hengxing Zhou Hengxing Zhou Hengxing Zhou Shiqing Feng Shiqing Feng Shiqing Feng Shiqing Feng |
| author_facet | Huan Jian Huan Jian Chi Zhang Chi Zhang ZhangYang Qi ZhangYang Qi Xueying Li Xueying Li Xueying Li Yongfu Lou Yongfu Lou Yi Kang Yi Kang Weimin Deng Yigang Lv Yigang Lv Chaoyu Wang Chaoyu Wang Wei Wang Wei Wang Shenghui Shang Shenghui Shang Mengfan Hou Mengfan Hou Hengxing Zhou Hengxing Zhou Hengxing Zhou Hengxing Zhou Shiqing Feng Shiqing Feng Shiqing Feng Shiqing Feng |
| author_sort | Huan Jian |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T04:51:33Z |
| format | Article |
| id | doaj.art-b24b0dba9b4f4918a53a8c650b96c89c |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-14T04:51:33Z |
| publishDate | 2021-02-01 |
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| series | Frontiers in Genetics |
| spelling | doaj.art-b24b0dba9b4f4918a53a8c650b96c89c2022-12-21T23:16:31ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-02-011210.3389/fgene.2021.633681633681Alteration of mRNA 5-Methylcytosine Modification in Neurons After OGD/R and Potential Roles in Cell Stress Response and ApoptosisHuan Jian0Huan Jian1Chi Zhang2Chi Zhang3ZhangYang Qi4ZhangYang Qi5Xueying Li6Xueying Li7Xueying Li8Yongfu Lou9Yongfu Lou10Yi Kang11Yi Kang12Weimin Deng13Yigang Lv14Yigang Lv15Chaoyu Wang16Chaoyu Wang17Wei Wang18Wei Wang19Shenghui Shang20Shenghui Shang21Mengfan Hou22Mengfan Hou23Hengxing Zhou24Hengxing Zhou25Hengxing Zhou26Hengxing Zhou27Shiqing Feng28Shiqing Feng29Shiqing Feng30Shiqing Feng31Department of Orthopaedics, Tianjin Medical University General Hospital, Tianjin, ChinaInternational Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Orthopaedics, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaShandong University Center for Orthopaedics, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Orthopaedics, Tianjin Medical University General Hospital, Tianjin, ChinaInternational Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Orthopaedics, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaShandong University Center for Orthopaedics, Cheeloo College of Medicine, Shandong University, Jinan, ChinaKey Laboratory of Immuno Microenvironment and Disease of the Educational Ministry of China, Department of Immunology, Tianjin Medical University, Tianjin, ChinaDepartment of Orthopaedics, Tianjin Medical University General Hospital, Tianjin, ChinaInternational Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Orthopaedics, Tianjin Medical University General Hospital, Tianjin, ChinaInternational Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin Medical University General Hospital, Tianjin, ChinaKey Laboratory of Immuno Microenvironment and Disease of the Educational Ministry of China, Department of Immunology, Tianjin Medical University, Tianjin, ChinaDepartment of Orthopaedics, Tianjin Medical University General Hospital, Tianjin, ChinaInternational Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Orthopaedics, Tianjin Medical University General Hospital, Tianjin, ChinaInternational Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Orthopaedics, Tianjin Medical University General Hospital, Tianjin, ChinaInternational Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Orthopaedics, Tianjin Medical University General Hospital, Tianjin, ChinaInternational Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Orthopaedics, Tianjin Medical University General Hospital, Tianjin, ChinaInternational Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Orthopaedics, Tianjin Medical University General Hospital, Tianjin, ChinaInternational Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Orthopaedics, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaShandong University Center for Orthopaedics, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Orthopaedics, Tianjin Medical University General Hospital, Tianjin, ChinaInternational Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Orthopaedics, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaShandong University Center for Orthopaedics, Cheeloo College of Medicine, Shandong University, Jinan, ChinaEpigenetic 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.https://www.frontiersin.org/articles/10.3389/fgene.2021.633681/fullm5C methylationepitranscriptomeischemia-reperfusion injuryoxygen-glucose deprivation/reoxygenationcell stressapoptosis |
| spellingShingle | Huan Jian Huan Jian Chi Zhang Chi Zhang ZhangYang Qi ZhangYang Qi Xueying Li Xueying Li Xueying Li Yongfu Lou Yongfu Lou Yi Kang Yi Kang Weimin Deng Yigang Lv Yigang Lv Chaoyu Wang Chaoyu Wang Wei Wang Wei Wang Shenghui Shang Shenghui Shang Mengfan Hou Mengfan Hou Hengxing Zhou Hengxing Zhou Hengxing Zhou Hengxing Zhou Shiqing Feng Shiqing Feng Shiqing Feng Shiqing Feng Alteration of mRNA 5-Methylcytosine Modification in Neurons After OGD/R and Potential Roles in Cell Stress Response and Apoptosis Frontiers in Genetics m5C methylation epitranscriptome ischemia-reperfusion injury oxygen-glucose deprivation/reoxygenation cell stress apoptosis |
| title | Alteration of mRNA 5-Methylcytosine Modification in Neurons After OGD/R and Potential Roles in Cell Stress Response and Apoptosis |
| title_full | Alteration of mRNA 5-Methylcytosine Modification in Neurons After OGD/R and Potential Roles in Cell Stress Response and Apoptosis |
| title_fullStr | Alteration of mRNA 5-Methylcytosine Modification in Neurons After OGD/R and Potential Roles in Cell Stress Response and Apoptosis |
| title_full_unstemmed | Alteration of mRNA 5-Methylcytosine Modification in Neurons After OGD/R and Potential Roles in Cell Stress Response and Apoptosis |
| title_short | Alteration of mRNA 5-Methylcytosine Modification in Neurons After OGD/R and Potential Roles in Cell Stress Response and Apoptosis |
| title_sort | alteration of mrna 5 methylcytosine modification in neurons after ogd r and potential roles in cell stress response and apoptosis |
| topic | m5C methylation epitranscriptome ischemia-reperfusion injury oxygen-glucose deprivation/reoxygenation cell stress apoptosis |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2021.633681/full |
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