通过内源标记赋权的单分子m6检测揭示了RNA异构体之间的复杂性
Wenbing Guo1, Zhijun Ren1, Xiang Huang1
1Department of Histoembryology and Cell Biology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou 510080, China; Medical College of Jiaying University, Meizhou 514031, China.
Molecular cell
|February 8, 2025
概括
这项研究介绍了m6Aiso,这是一种用于在RNA上映射N6-甲基氨酸 (m6A) 的深度学习模型. m6Aiso揭示了RNA异形中m6A模式,包括距离依赖的链接和异形特异性甲基化.
科学领域:
- 分子生物学分子生物学
- 基因组学就是基因组学.
- 生物信息学是一种生物信息学.
背景情况:
- N6-甲基氨酸 (m6A) 是一种关键的RNA修饰,但其在多种RNA异型中分布仍然不清楚.
- 了解m6A动态对于破译基因调节和细胞过程至关重要.
研究的目的:
- 开发一种高分辨率的方法,用于在单个RNA分子和异型中映射m6A位点.
- 在不同RNA环境中研究m6A修饰的调节机制和模式.
主要方法:
- 在牛津纳米孔技术 (ONT) 上使用APOBEC1-YTH诱导的C-to-U突变对m6A位点进行内源标记直接RNA测序 (DRS) 读取.
- 开发和应用m6Aiso,一个深度残留神经网络,用于单读m6A的识别和量化.
- 在RNA异形中分析m6A模式,包括距离依赖的链接和异形特异性甲基化.
主要成果:
- 产生了超过100万个单读m6A信号,使得精确的映射.
- 在一次性读取分辨率下,m6A网站被准确地识别和量化.
- 发现了依赖于距离的m6A位点链接和在内部保留异型体上的特定甲基化,这些异型体受外因子结点附近和TARBP2结合的影响.
- 鉴定了SMAD3作为在上皮层-介质酶过渡期间m6A沉积的促进剂,影响替代促进剂驱动的异型.
结论:
- m6Aiso提供了一种有效的工具,用于剖析RNA异型中m6A修饰的复杂景观.
- 这项研究揭示了对m6A调节的新见解,包括异形特异性甲基化和SMAD3.3等转录因子的作用.
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