Abstract
Background: N6-Methyladenosine (m6A) 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 m6A in NMOSD patients. Methods: This study assessed the m6A 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 m6A 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 m6A level. Differential m6A 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 m6A methylation may act on functional genes to regulate immune homeostasis in NMOSD.
Highlights
N6-Methyladenosine (m6A) is one of the most abundant internal modifications of eukaryotic messenger RNA and plays an important role in gene expression regulatory processes, including the maintenance of stability, splicing and translation (Chen et al, 2019a)
Methyltransferase Like 3 (METTL3) catalyses the production of m6A; methyltransferase-like 14 (METTL4) forms a complex with METTL3, participates in interactions with target messenger RNA (mRNA) and recruits RNA, and Wilms tumour 1-associated protein (WTAP) stabilizes the complex (Liu et al, 2014; Ping et al, 2014; Lin et al, 2016)
We found that the m6A level was much lower in patients than in healthy controls (HCs), demonstrating that m6A modification is very important in the process of neuromyelitis optica spectrum disorders (NMOSD)
Summary
N6-Methyladenosine (m6A) is one of the most abundant internal modifications of eukaryotic messenger RNA (mRNA) and plays an important role in gene expression regulatory processes, including the maintenance of stability, splicing and translation (Chen et al, 2019a). Readers, including YTH N6 methyladenosine RNA-binding protein 1–3 (YTHDF1-3) and insulin-like growth factor 2 mRNAbinding protein 1–3 (IGF2BP1-3), are necessary for this process (Wang et al, 2014; Wang et al, 2015; Hanniford et al, 2020). These proteins recognize sites of mRNA methylation and affect RNA metabolism directly or indirectly. Its role in neuromyelitis optica spectrum disorders (NMOSD) is not known
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