Screen of traumatic brain injury-associated genes from lncRNA m6A-modified transcriptomes in the cerebral cortex of mice after repetitive mild traumatic brain injury

N6-methyladenosine (m6A), a prevalent post-transcriptional modification in eukaryotic RNA, plays a significant role in regulating sensory experiences, learning, and injury in the mammalian central nervous system. However, the pattern of lncRNA m6A methylation in the mouse cortex following repetitive mild traumatic brain injury (rmTBI) has not been explored. This study conducted a genome-wide analysis of lncRNA m6A methylation in the mouse cortex using methylated RNA immunoprecipitation sequencing (MeRIP-Seq). Our analysis revealed 43,103 peaks were significantly upregulated or downregulated. Notably, the expression of m6A peaks indicated altered methylation and expression levels of 423 lncRNAs after rmTBI. In addition, employing METTL3 inhibitor STM2457 demonstrated that functional METTL3 was essential for repairing neural damage caused by rmTBI and influenced spatial learning and memory in rmTBI-model mice. Thus, the m6A methylation pattern of lncRNA in the mouse cortex after rmTBI identifies METTL3 as a potential intervention target for epigenetic modification following such injuries. This study conducted a genome-wide analysis of lncRNA m6A methylation in the mouse cortex via methylated RNA immunoprecipitation sequencing (MeRIP-Seq). In addition, by using the METTL3 inhibitor STM2457, functional METTL3 was found to be necessary for repairing neural damage caused by rmTBI and to affect spatial learning and memory in rmTBI-model mice.