线粒体Mrna m6 A修饰图谱及其在神经发育与脑肿瘤中的相关变化OA

Objective To systematically characterize N6-methyladenosine(m6A)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 m6A profiling techniques were integrated to com-pare m6A distribution and relative methylation levels across chromosomes and to delineate an m6A modification land-scape 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 immu-noprecipitation followed by quantitative polymerase chain reaction(MeRIP-qPCR).Results m6A 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 m6A levels showed stage-dependent changes.Compared with normal brain tissues,mt-mRNA m6A levels were decreased in glio-blastoma and medulloblastoma.Conclusions This study confirms the presence of m6A modifications in the mitochon-drial 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.