Center for Precision Medicine, School of Medicine and School of Biomedical Sciences, Huaqiao University, Xiamen 361021, China.
School of Life Sciences and Technology, Shanghai Jiao Tong University, Shanghai 200240, China.
Genes (Basel). 2020 Sep 27;11(10):1139. doi: 10.3390/genes11101139.
N-methyladenosine (mA)-mediated epitranscriptomic regulation is critical for various physiological processes. Genetic studies demonstrate that proper mA-methylation is required for mouse brain development and function. Revealing landscapes of mA-methylation in the cerebral cortex at different developmental stages will help to understand the biological meaning of epitranscriptomic regulation. Here, we depict the temporal-specific mA-methylation status in mouse embryonic and postnatal cortices using methylated RNA immunoprecipitation (MeRIP) sequencing. We identified unique mA binding motifs in stage-specific RNAs and found that more RNA transcripts are temporally methylated in embryonic cortices than in postnatal ones. Moreover, we found that cortical transcription factors and genes associated with neurological disorders are broadly as well specifically methylated at mA sites. Our study highlights the importance of epitranscriptomic regulation in the developing cortex and provides a fundamental reference for future mechanistic examinations of mA methylation-mediated gene expression regulation in normal brain development and neurological disorders.
N6-甲基腺苷（m6A）介导的转录后修饰对于各种生理过程至关重要。遗传研究表明，m6A 甲基化的适当修饰对于小鼠大脑的发育和功能是必需的。揭示不同发育阶段大脑皮层中 m6A 甲基化的图谱将有助于理解转录后修饰的生物学意义。在这里，我们使用 m6A 免疫沉淀测序（MeRIP-seq）描绘了小鼠胚胎和出生后皮质中时间特异性的 m6A 甲基化状态。我们在阶段特异性 RNA 中鉴定出独特的 m6A 结合基序，并发现胚胎皮质中被 m6A 修饰的 RNA 转录本比出生后皮质中的更多。此外，我们发现皮质转录因子和与神经紊乱相关的基因在 m6A 位点广泛且特异性地被甲基化。我们的研究强调了转录后修饰在发育中的皮质中的重要性，并为未来正常大脑发育和神经紊乱中 m6A 甲基化介导的基因表达调控的机制研究提供了基础参考。
