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 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.