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N(1)-Methyladenosine modification of mRNA regulates neuronal gene expression and oxygen glucose deprivation/reoxygenation induction

N(1)-Methyladenosine (m1A) is an abundant modification of transcripts, plays important roles in regulating mRNA structure and translation efficiency, and is dynamically regulated under stress. However, the characteristics and functions of mRNA m1A modification in primary neurons and oxygen glucose d...

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Autores principales: Qi, Zhangyang, Zhang, Chi, Jian, Huan, Hou, Mengfan, Lou, Yongfu, Kang, Yi, Wang, Wei, Lv, Yigang, Shang, Shenghui, Wang, Chaoyu, Li, Xueying, Feng, Shiqing, Zhou, Hengxing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10182019/
https://www.ncbi.nlm.nih.gov/pubmed/37173310
http://dx.doi.org/10.1038/s41420-023-01458-2
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author Qi, Zhangyang
Zhang, Chi
Jian, Huan
Hou, Mengfan
Lou, Yongfu
Kang, Yi
Wang, Wei
Lv, Yigang
Shang, Shenghui
Wang, Chaoyu
Li, Xueying
Feng, Shiqing
Zhou, Hengxing
author_facet Qi, Zhangyang
Zhang, Chi
Jian, Huan
Hou, Mengfan
Lou, Yongfu
Kang, Yi
Wang, Wei
Lv, Yigang
Shang, Shenghui
Wang, Chaoyu
Li, Xueying
Feng, Shiqing
Zhou, Hengxing
author_sort Qi, Zhangyang
collection PubMed
description N(1)-Methyladenosine (m1A) is an abundant modification of transcripts, plays important roles in regulating mRNA structure and translation efficiency, and is dynamically regulated under stress. However, the characteristics and functions of mRNA m1A modification in primary neurons and oxygen glucose deprivation/reoxygenation (OGD/R) induced remain unclear. We first constructed a mouse cortical neuron OGD/R model and then used methylated RNA immunoprecipitation (MeRIP) and sequencing technology to demonstrate that m1A modification is abundant in neuron mRNAs and dynamically regulated during OGD/R induction. Our study suggests that Trmt10c, Alkbh3, and Ythdf3 may be m1A-regulating enzymes in neurons during OGD/R induction. The level and pattern of m1A modification change significantly during OGD/R induction, and differential methylation is closely associated with the nervous system. Our findings show that m1A peaks in cortical neurons aggregate at both the 5’ and 3’ untranslated regions. m1A modification can regulate gene expression, and peaks in different regions have different effects on gene expression. By analysing m1A-seq and RNA-seq data, we show a positive correlation between differentially methylated m1A peaks and gene expression. The correlation was verified by using qRT-PCR and MeRIP-RT-PCR. Moreover, we selected human tissue samples from Parkinson’s disease (PD) and Alzheimer’s disease (AD) patients from the Gene Expression Comprehensive (GEO) database to analyse the selected differentially expressed genes (DEGs) and differential methylation modification regulatory enzymes, respectively, and found similar differential expression results. We highlight the potential relationship between m1A modification and neuronal apoptosis following OGD/R induction. Furthermore, by mapping mouse cortical neurons and OGD/R-induced modification characteristics, we reveal the important role of m1A modification in OGD/R and gene expression regulation, providing new ideas for research on neurological damage.
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spelling pubmed-101820192023-05-14 N(1)-Methyladenosine modification of mRNA regulates neuronal gene expression and oxygen glucose deprivation/reoxygenation induction Qi, Zhangyang Zhang, Chi Jian, Huan Hou, Mengfan Lou, Yongfu Kang, Yi Wang, Wei Lv, Yigang Shang, Shenghui Wang, Chaoyu Li, Xueying Feng, Shiqing Zhou, Hengxing Cell Death Discov Article N(1)-Methyladenosine (m1A) is an abundant modification of transcripts, plays important roles in regulating mRNA structure and translation efficiency, and is dynamically regulated under stress. However, the characteristics and functions of mRNA m1A modification in primary neurons and oxygen glucose deprivation/reoxygenation (OGD/R) induced remain unclear. We first constructed a mouse cortical neuron OGD/R model and then used methylated RNA immunoprecipitation (MeRIP) and sequencing technology to demonstrate that m1A modification is abundant in neuron mRNAs and dynamically regulated during OGD/R induction. Our study suggests that Trmt10c, Alkbh3, and Ythdf3 may be m1A-regulating enzymes in neurons during OGD/R induction. The level and pattern of m1A modification change significantly during OGD/R induction, and differential methylation is closely associated with the nervous system. Our findings show that m1A peaks in cortical neurons aggregate at both the 5’ and 3’ untranslated regions. m1A modification can regulate gene expression, and peaks in different regions have different effects on gene expression. By analysing m1A-seq and RNA-seq data, we show a positive correlation between differentially methylated m1A peaks and gene expression. The correlation was verified by using qRT-PCR and MeRIP-RT-PCR. Moreover, we selected human tissue samples from Parkinson’s disease (PD) and Alzheimer’s disease (AD) patients from the Gene Expression Comprehensive (GEO) database to analyse the selected differentially expressed genes (DEGs) and differential methylation modification regulatory enzymes, respectively, and found similar differential expression results. We highlight the potential relationship between m1A modification and neuronal apoptosis following OGD/R induction. Furthermore, by mapping mouse cortical neurons and OGD/R-induced modification characteristics, we reveal the important role of m1A modification in OGD/R and gene expression regulation, providing new ideas for research on neurological damage. Nature Publishing Group UK 2023-05-12 /pmc/articles/PMC10182019/ /pubmed/37173310 http://dx.doi.org/10.1038/s41420-023-01458-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Qi, Zhangyang
Zhang, Chi
Jian, Huan
Hou, Mengfan
Lou, Yongfu
Kang, Yi
Wang, Wei
Lv, Yigang
Shang, Shenghui
Wang, Chaoyu
Li, Xueying
Feng, Shiqing
Zhou, Hengxing
N(1)-Methyladenosine modification of mRNA regulates neuronal gene expression and oxygen glucose deprivation/reoxygenation induction
title N(1)-Methyladenosine modification of mRNA regulates neuronal gene expression and oxygen glucose deprivation/reoxygenation induction
title_full N(1)-Methyladenosine modification of mRNA regulates neuronal gene expression and oxygen glucose deprivation/reoxygenation induction
title_fullStr N(1)-Methyladenosine modification of mRNA regulates neuronal gene expression and oxygen glucose deprivation/reoxygenation induction
title_full_unstemmed N(1)-Methyladenosine modification of mRNA regulates neuronal gene expression and oxygen glucose deprivation/reoxygenation induction
title_short N(1)-Methyladenosine modification of mRNA regulates neuronal gene expression and oxygen glucose deprivation/reoxygenation induction
title_sort n(1)-methyladenosine modification of mrna regulates neuronal gene expression and oxygen glucose deprivation/reoxygenation induction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10182019/
https://www.ncbi.nlm.nih.gov/pubmed/37173310
http://dx.doi.org/10.1038/s41420-023-01458-2
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