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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Main Authors: 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
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Language:English
Published: eLife Sciences Publications Ltd 2023-03-01
Series:eLife
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Online Access:https://elifesciences.org/articles/85324
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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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