摘要
目的系统鉴定线粒体mRNA(mt-mRNA)上的N^(6)-甲基腺苷(m^(6)A)修饰,解析其修饰图谱,并分析其在神经发育及脑肿瘤中的变化。方法整合来自7种m^(6)A检测技术的13套测序数据,比较各染色体m^(6)A分布与相对甲基化水平,揭示mt-mRNA的m^(6)A修饰特征。同时收集处于不同发育阶段的小鼠大脑皮质、小脑组织及3种脑肿瘤细胞系,采用甲基化RNA免疫共沉淀联合定量聚合酶链式反应(MeRIP-qPCR)验证代表性转录本的m^(6)A水平。结果在人、小鼠和大鼠的多种组织与细胞中均检测到mt-mRNA的m^(6)A信号,但整体水平低于核转录本。在小鼠大脑皮质和小脑发育过程中,mt-mRNA的m^(6)A水平呈动态变化。与正常组织相比,胶质母细胞瘤和髓母细胞瘤中mt-mRNA的m^(6)A水平下调。结论本研究证实线粒体转录组中存在m^(6)A修饰,并在神经发育和脑肿瘤中呈动态变化,为阐明线粒体功能及相关疾病中的作用提供了新的视角。
Objective To systematically characterize N^(6)-methyladenosine(m^(6)A)modifications on mitochondrial messenger RNA(mt-mRNA),define its features,and investigate its changes during neurodevelopment and in brain tumors.Methods Thirteen sequencing datasets generated by seven m^(6)A profiling techniques were integrated to compare m^(6)A distribution and relative methylation levels across chromosomes and to delineate an m^(6)A modification landscape of mt-mRNA.In addition,mouse cerebral cortices and cerebella at different developmental stages,together with three brain tumor cell lines,were collected,and representative transcripts were validated by methylated RNA immunoprecipitation followed by quantitative polymerase chain reaction(MeRIP-qPCR).Results m^(6)A modifications on mt-mRNA were detected across multiple human,mouse and rat tissues and cell types,albeit at levels lower than those of nuclear-encoded transcripts.During mouse cortical and cerebellar development,mt-mRNA m^(6)A levels showed stage-dependent changes.Compared with normal brain tissues,mt-mRNA m^(6)A levels were decreased in glioblastoma and medulloblastoma.Conclusions This study confirms the presence of m^(6)A modifications in the mitochondrial transcriptome and demonstrates their dynamic regulation during neurodevelopment and in the pathogenesis of brain tumors,providing a new perspective for understanding mitochondrial function and its involvement in diseases.
作者
付玉洁
潘文琦
杨林
滕徐菲
宋述慧
佟伟民
牛亚梅
FU Yujie;PAN Wenqi;YANG Lin;TENG Xufei;SONG Shuhui;TONG Weimin;NIU Yamei(Department of Pathology,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100005;Beijing Institute of Genomics,Chinese Academy of Sciences,Beijing 100101,China)
出处
《基础医学与临床》
2026年第4期504-511,共8页
Basic and Clinical Medicine
基金
中国医学科学院医学与健康科学创新工程(2021-I2M-1-020)。
