The landscape of m1A modification and its posttranscriptional regulatory functions in primary neurons
Cerebral ischaemia‒reperfusion injury (IRI), during which neurons undergo oxygen-glucose deprivation/reoxygenation (OGD/R), is a notable pathological process in many neurological diseases. N1-methyladenosine (m1A) is an RNA modification that can affect gene expression and RNA stability. The m1A land...
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eLife Sciences Publications Ltd
2023-03-01
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author | Chi Zhang Xianfu Yi Mengfan Hou Qingyang Li Xueying Li Lu Lu Enlin Qi Mingxin Wu Lin Qi Huan Jian Zhangyang Qi Yigang Lv Xiaohong Kong Mingjun Bi Shiqing Feng Hengxing Zhou |
author_facet | Chi Zhang Xianfu Yi Mengfan Hou Qingyang Li Xueying Li Lu Lu Enlin Qi Mingxin Wu Lin Qi Huan Jian Zhangyang Qi Yigang Lv Xiaohong Kong Mingjun Bi Shiqing Feng Hengxing Zhou |
author_sort | Chi Zhang |
collection | DOAJ |
description | Cerebral ischaemia‒reperfusion injury (IRI), during which neurons undergo oxygen-glucose deprivation/reoxygenation (OGD/R), is a notable pathological process in many neurological diseases. N1-methyladenosine (m1A) is an RNA modification that can affect gene expression and RNA stability. The m1A landscape and potential functions of m1A modification in neurons remain poorly understood. We explored RNA (mRNA, lncRNA, and circRNA) m1A modification in normal and OGD/R-treated mouse neurons and the effect of m1A on diverse RNAs. We investigated the m1A landscape in primary neurons, identified m1A-modified RNAs, and found that OGD/R increased the number of m1A RNAs. m1A modification might also affect the regulatory mechanisms of noncoding RNAs, e.g., lncRNA–RNA binding proteins (RBPs) interactions and circRNA translation. We showed that m1A modification mediates the circRNA/lncRNA‒miRNA–mRNA competing endogenous RNA (ceRNA) mechanism and that 3' untranslated region (3’UTR) modification of mRNAs can hinder miRNA–mRNA binding. Three modification patterns were identified, and genes with different patterns had intrinsic mechanisms with potential m1A-regulatory specificity. Systematic analysis of the m1A landscape in normal and OGD/R neurons lays a critical foundation for understanding RNA modification and provides new perspectives and a theoretical basis for treating and developing drugs for OGD/R pathology-related diseases. |
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spelling | doaj.art-18ef5061ccba4b47b9a4dd1b77114d472023-07-25T14:03:59ZengeLife Sciences Publications LtdeLife2050-084X2023-03-011210.7554/eLife.85324The landscape of m1A modification and its posttranscriptional regulatory functions in primary neuronsChi Zhang0https://orcid.org/0000-0003-1288-9006Xianfu Yi1Mengfan Hou2Qingyang Li3Xueying Li4Lu Lu5Enlin Qi6Mingxin Wu7Lin Qi8Huan Jian9Zhangyang Qi10Yigang Lv11Xiaohong Kong12Mingjun Bi13https://orcid.org/0000-0001-8748-2636Shiqing Feng14Hengxing Zhou15https://orcid.org/0000-0003-0053-8970Department of Orthopaedics, Qilu Hospital of Shandong University, Shandong University Centre for Orthopaedics, Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Bioinformatics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, ChinaDepartment of Orthopaedics, Tianjin Medical University General Hospital, International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin, ChinaDepartment of Orthopaedics, Qilu Hospital of Shandong University, Shandong University Centre for Orthopaedics, Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Orthopaedics, Qilu Hospital of Shandong University, Shandong University Centre for Orthopaedics, Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Orthopaedics, Tianjin Medical University General Hospital, International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin, ChinaDepartment of Orthopaedics, Qilu Hospital of Shandong University, Shandong University Centre for Orthopaedics, Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Orthopaedics, Tianjin Medical University General Hospital, International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin, ChinaDepartment of Orthopedics, Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Orthopaedics, Tianjin Medical University General Hospital, International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin, ChinaDepartment of Orthopaedics, Qilu Hospital of Shandong University, Shandong University Centre for Orthopaedics, Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Orthopaedics, Tianjin Medical University General Hospital, International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin, ChinaDepartment of Orthopaedics, Qilu Hospital of Shandong University, Shandong University Centre for Orthopaedics, Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Orthopaedics, Qilu Hospital of Shandong University, Shandong University Centre for Orthopaedics, Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Orthopaedics, Qilu Hospital of Shandong University, Shandong University Centre for Orthopaedics, Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, China; Department of Orthopaedics, Tianjin Medical University General Hospital, International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin, ChinaDepartment of Orthopaedics, Qilu Hospital of Shandong University, Shandong University Centre for Orthopaedics, Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, China; Department of Orthopaedics, Tianjin Medical University General Hospital, International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin, ChinaCerebral ischaemia‒reperfusion injury (IRI), during which neurons undergo oxygen-glucose deprivation/reoxygenation (OGD/R), is a notable pathological process in many neurological diseases. N1-methyladenosine (m1A) is an RNA modification that can affect gene expression and RNA stability. The m1A landscape and potential functions of m1A modification in neurons remain poorly understood. We explored RNA (mRNA, lncRNA, and circRNA) m1A modification in normal and OGD/R-treated mouse neurons and the effect of m1A on diverse RNAs. We investigated the m1A landscape in primary neurons, identified m1A-modified RNAs, and found that OGD/R increased the number of m1A RNAs. m1A modification might also affect the regulatory mechanisms of noncoding RNAs, e.g., lncRNA–RNA binding proteins (RBPs) interactions and circRNA translation. We showed that m1A modification mediates the circRNA/lncRNA‒miRNA–mRNA competing endogenous RNA (ceRNA) mechanism and that 3' untranslated region (3’UTR) modification of mRNAs can hinder miRNA–mRNA binding. Three modification patterns were identified, and genes with different patterns had intrinsic mechanisms with potential m1A-regulatory specificity. Systematic analysis of the m1A landscape in normal and OGD/R neurons lays a critical foundation for understanding RNA modification and provides new perspectives and a theoretical basis for treating and developing drugs for OGD/R pathology-related diseases.https://elifesciences.org/articles/85324epitranscriptomicsneuronm1A modificationOGDncRNA |
spellingShingle | Chi Zhang Xianfu Yi Mengfan Hou Qingyang Li Xueying Li Lu Lu Enlin Qi Mingxin Wu Lin Qi Huan Jian Zhangyang Qi Yigang Lv Xiaohong Kong Mingjun Bi Shiqing Feng Hengxing Zhou The landscape of m1A modification and its posttranscriptional regulatory functions in primary neurons eLife epitranscriptomics neuron m1A modification OGD ncRNA |
title | The landscape of m1A modification and its posttranscriptional regulatory functions in primary neurons |
title_full | The landscape of m1A modification and its posttranscriptional regulatory functions in primary neurons |
title_fullStr | The landscape of m1A modification and its posttranscriptional regulatory functions in primary neurons |
title_full_unstemmed | The landscape of m1A modification and its posttranscriptional regulatory functions in primary neurons |
title_short | The landscape of m1A modification and its posttranscriptional regulatory functions in primary neurons |
title_sort | landscape of m1a modification and its posttranscriptional regulatory functions in primary neurons |
topic | epitranscriptomics neuron m1A modification OGD ncRNA |
url | https://elifesciences.org/articles/85324 |
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