Department of Neurology, The First Rehabilitation Hospital of Shanghai, School of Medicine, Tongji University, Shanghai, China.
Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Mol Neurobiol. 2024 Mar;61(3):1781-1793. doi: 10.1007/s12035-023-03643-x. Epub 2023 Sep 30.
Researchers have recently found that N-methyladenosine (mA) is a type of internal posttranscriptional modification that is essential in mammalian mRNA. However, the features of mA RNA methylation in acute intracerebral hemorrhage (ICH) remain unknown. To explore differential methylations and to discover their functions in acute ICH patients, we recruited three acute ICH patients, three healthy controls, and an additional three patients and healthy controls for validation. The mA methylation levels in blood samples from the two groups were determined by ultrahigh-performance liquid chromatography coupled with triple quadruple mass spectrometry (UPLC-QQQ-MS). Methylated RNA immunoprecipitation sequencing (MeRIP-seq) was employed to identify differences in mA modification, and the differentially expressed mA-modified genes were confirmed by MeRIP-qPCR. We found no significant differences in the total mA levels between the two groups but observed differential methylation peaks. Compared with the control group, the coding genes showing increased methylation following acute ICH were mostly involved in processes connected with osteoclast differentiation, the neurotrophin signaling pathway, and the spliceosome, whereas genes with reduced mA modification levels after acute ICH were found to be involved in the B-cell and T-cell receptor signaling pathways. These results reveal that differentially mA-modified genes may influence the immune microenvironments in acute ICH.
研究人员最近发现，N6-甲基腺苷（m6A）是一种在哺乳动物 mRNA 中至关重要的内部转录后修饰类型。然而，急性脑出血（ICH）中 mA RNA 甲基化的特征尚不清楚。为了探讨差异甲基化及其在急性 ICH 患者中的功能，我们招募了 3 名急性 ICH 患者、3 名健康对照者，以及另外 3 名患者和健康对照者进行验证。通过超高效液相色谱与三重四极杆质谱联用（UPLC-QQQ-MS）测定两组血样中的 mA 甲基化水平。采用甲基化 RNA 免疫沉淀测序（MeRIP-seq）鉴定 mA 修饰的差异，并通过 MeRIP-qPCR 验证差异表达的 mA 修饰基因。我们发现两组之间总 mA 水平没有显著差异，但观察到差异甲基化峰。与对照组相比，急性 ICH 后甲基化增加的编码基因大多参与破骨细胞分化、神经营养因子信号通路和剪接体相关的过程，而急性 ICH 后 mA 修饰水平降低的基因则参与 B 细胞和 T 细胞受体信号通路。这些结果表明，差异 mA 修饰基因可能影响急性 ICH 中的免疫微环境。
