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Comprehensive Analysis of N(6)-Methyladenosine (m(6)A) Methylation in Neuromyelitis Optica Spectrum Disorders

Background: N(6)-Methyladenosine (m(6)A) methylation is the most prevalent internal posttranscriptional modification on mammalian mRNA. But its role in neuromyelitis optica spectrum disorders (NMOSD) is not known. Aims: To explore the mechanism of m(6)A in NMOSD patients. Methods: This study assesse...

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Autores principales: Yang, Hong, Wu, Yi-Fan, Ding, Jie, Liu, Wei, Zhu, De-Sheng, Shen, Xia-Feng, Guan, Yang-Tai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8660110/
https://www.ncbi.nlm.nih.gov/pubmed/34899833
http://dx.doi.org/10.3389/fgene.2021.735454
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author Yang, Hong
Wu, Yi-Fan
Ding, Jie
Liu, Wei
Zhu, De-Sheng
Shen, Xia-Feng
Guan, Yang-Tai
author_facet Yang, Hong
Wu, Yi-Fan
Ding, Jie
Liu, Wei
Zhu, De-Sheng
Shen, Xia-Feng
Guan, Yang-Tai
author_sort Yang, Hong
collection PubMed
description Background: N(6)-Methyladenosine (m(6)A) methylation is the most prevalent internal posttranscriptional modification on mammalian mRNA. But its role in neuromyelitis optica spectrum disorders (NMOSD) is not known. Aims: To explore the mechanism of m(6)A in NMOSD patients. Methods: This study assessed the m(6)A methylation levels in blood from two groups: NMOSD patients and healthy controls. Methylated RNA immunoprecipitation Sequencing (MeRIP-seq) and RNA-seq were performed to assess differences in m(6)A methylation between NMOSD patients and healthy controls. Ultra-high performance liquid chromatography coupled with triple quadruple mass spectrometry (UPLC-QQQ-MS) method was performed to check m(6)A level. Differential m(6)A methylation genes were validated by MeRIP-qPCR. Results: Compared with that in the control group, the total m6A level was decreased in the NMOSD group. Genes with upregulated methylation were primarily enriched in processes associated with RNA splicing, mRNA processing, and innate immune response, while genes with downregulated methylation were enriched in processes associated with the regulation of transcription, DNA-templating, and the positive regulation of I-kappa B kinase/NF-kappa B signalling. Conclusion: These findings demonstrate that differential m(6)A methylation may act on functional genes to regulate immune homeostasis in NMOSD.
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spelling pubmed-86601102021-12-10 Comprehensive Analysis of N(6)-Methyladenosine (m(6)A) Methylation in Neuromyelitis Optica Spectrum Disorders Yang, Hong Wu, Yi-Fan Ding, Jie Liu, Wei Zhu, De-Sheng Shen, Xia-Feng Guan, Yang-Tai Front Genet Genetics Background: N(6)-Methyladenosine (m(6)A) methylation is the most prevalent internal posttranscriptional modification on mammalian mRNA. But its role in neuromyelitis optica spectrum disorders (NMOSD) is not known. Aims: To explore the mechanism of m(6)A in NMOSD patients. Methods: This study assessed the m(6)A methylation levels in blood from two groups: NMOSD patients and healthy controls. Methylated RNA immunoprecipitation Sequencing (MeRIP-seq) and RNA-seq were performed to assess differences in m(6)A methylation between NMOSD patients and healthy controls. Ultra-high performance liquid chromatography coupled with triple quadruple mass spectrometry (UPLC-QQQ-MS) method was performed to check m(6)A level. Differential m(6)A methylation genes were validated by MeRIP-qPCR. Results: Compared with that in the control group, the total m6A level was decreased in the NMOSD group. Genes with upregulated methylation were primarily enriched in processes associated with RNA splicing, mRNA processing, and innate immune response, while genes with downregulated methylation were enriched in processes associated with the regulation of transcription, DNA-templating, and the positive regulation of I-kappa B kinase/NF-kappa B signalling. Conclusion: These findings demonstrate that differential m(6)A methylation may act on functional genes to regulate immune homeostasis in NMOSD. Frontiers Media S.A. 2021-11-11 /pmc/articles/PMC8660110/ /pubmed/34899833 http://dx.doi.org/10.3389/fgene.2021.735454 Text en Copyright © 2021 Yang, Wu, Ding, Liu, Zhu, Shen and Guan. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Yang, Hong
Wu, Yi-Fan
Ding, Jie
Liu, Wei
Zhu, De-Sheng
Shen, Xia-Feng
Guan, Yang-Tai
Comprehensive Analysis of N(6)-Methyladenosine (m(6)A) Methylation in Neuromyelitis Optica Spectrum Disorders
title Comprehensive Analysis of N(6)-Methyladenosine (m(6)A) Methylation in Neuromyelitis Optica Spectrum Disorders
title_full Comprehensive Analysis of N(6)-Methyladenosine (m(6)A) Methylation in Neuromyelitis Optica Spectrum Disorders
title_fullStr Comprehensive Analysis of N(6)-Methyladenosine (m(6)A) Methylation in Neuromyelitis Optica Spectrum Disorders
title_full_unstemmed Comprehensive Analysis of N(6)-Methyladenosine (m(6)A) Methylation in Neuromyelitis Optica Spectrum Disorders
title_short Comprehensive Analysis of N(6)-Methyladenosine (m(6)A) Methylation in Neuromyelitis Optica Spectrum Disorders
title_sort comprehensive analysis of n(6)-methyladenosine (m(6)a) methylation in neuromyelitis optica spectrum disorders
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8660110/
https://www.ncbi.nlm.nih.gov/pubmed/34899833
http://dx.doi.org/10.3389/fgene.2021.735454
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