在单细胞中对m6A的异型表征确定了它在RNA监测中的作用
Zhijun Ren1,2,3, Jialiang He1,2, Xiang Huang1,2,3
1Department of Histoembryology and Cell Biology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Nature communications
|July 2, 2025
概括
我们开发了m6A-isoSC-seq以在单细胞中研究N6-甲基氨酸 (m6A). 这种方法揭示了RNA异形和单细胞中的显著m6A异质性,突出了它在RNA监测中的作用.
科学领域:
- 分子生物学分子生物学
- 基因组学就是基因组学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 跨RNA异构体的N6-甲基氨酸 (m6A) 修饰的分布和单细胞异质性仍然不太清楚.
- m6A 是一个关键的表皮转录体标记,影响RNA代谢和功能.
研究的目的:
- 开发一种新的方法,m6A-isoSC-seq,用于高分辨率地图的m6A修改在单细胞RNA异型.
- 在异形和单细胞水平上研究m6A分布的异质性.
- 阐明m6A在RNA监测中的作用,特别是涉及错误处理的RNA异型.
主要方法:
- 开发m6A-isoSC-seq,集成牛津纳米孔长读和Illumina短读测序在10x Genomics单细胞cDNA库上.
- 利用APOBEC1-YTH诱导的m6A位点附近的C-to-U突变进行检测.
- 将该方法应用于来自三个细胞系的组合样本.
主要成果:
- m6A-isoSC-seq显示了RNA异型和单个细胞内的大量m6A异质性.
- 在错误处理的RNA异形上发现了广泛的,特定的m6A甲基化.
- 与编码异型相比,高甲基化错误处理的RNA异型对METTL3枯竭的敏感性增加.
- 观察到这些错误处理的RNA往往在编码区域中含有过多的m6A位点,使它们成为CDS-m6A衰变 (CMD) 的目标.
结论:
- 在RNA异形和单细胞水平上,m6A修饰表现出显著的异质性.
- 错误处理的RNA单体是特定的甲基化,对m6A调节剂敏感.
- m6A在RNA监测途径中发挥着关键作用,可能通过向错误处理的RNA通过CMD降解来降解.
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