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重复性轻度创伤性脑损伤后小鼠皮质中lncRNA m6A甲基化的全基因组分析

Genome-wide analysis of lncRNA m6A methylation in the mouse cortex after repetitive mild traumatic brain injury.

作者信息

Zhong Rongrong, Chen Chen, Zhang Yingao, Wang Conglin, Li Meimei, Chen Fanglian, Wang Lu, Liu Qiang, Lei Ping

机构信息

Deparment of Geriatrics, Tianjin Medical University General Hospital, No. 154, Anshan Road, Nanyingmen Street, Heping District, Tianjin, 300052, China.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China.

出版信息

BMC Genomics. 2025 May 20;26(1):509. doi: 10.1186/s12864-025-11696-6.

Abstract

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). We identified 43,103 differentially methylated peaks. 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. Clinical trial number Not applicable.

摘要

N6-甲基腺苷(m6A)是真核生物RNA中一种普遍的转录后修饰,在调节哺乳动物中枢神经系统的感觉体验、学习和损伤方面发挥着重要作用。然而,重复性轻度创伤性脑损伤(rmTBI)后小鼠皮质中长链非编码RNA(lncRNA)的m6A甲基化模式尚未得到探索。本研究使用甲基化RNA免疫沉淀测序(MeRIP-Seq)对小鼠皮质中的lncRNA m6A甲基化进行了全基因组分析。我们鉴定出43103个差异甲基化峰。值得注意的是,m6A峰的表达表明rmTBI后423个lncRNA的甲基化和表达水平发生了改变。此外,使用甲基转移酶样蛋白3(METTL3)抑制剂STM2457表明,功能性METTL3对于修复rmTBI造成的神经损伤至关重要,并影响rmTBI模型小鼠的空间学习和记忆。因此,rmTBI后小鼠皮质中lncRNA的m6A甲基化模式确定METTL3为此类损伤后表观遗传修饰的潜在干预靶点。临床试验编号不适用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2ad/12090626/214efdd14009/12864_2025_11696_Fig1_HTML.jpg

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