莫多拉多:通过非标签使用修改调用器来增强纳米孔测序中tRNA修改的检测
Franziskus N M Rübsam1, Wang Liu-Wei2,3,4, Yu Sun1
1Institut für Biologie, Lebenswissenschaftliche Fakultät, Humboldt-Universität zu Berlin, 10115 Berlin, Germany.
Nucleic acids research
|August 19, 2025
概括
研究人员使用纳米孔测序绘制了转移RNA (tRNA) 修改的地图,并开发了MoDorado来检测新网站. 这扩大了我们对tRNA修饰及其在细胞过程中的作用的理解.
科学领域:
- 分子生物学分子生物学
- 基因组学就是基因组学.
- 生物化学 生化学
背景情况:
- 精确识别转移RNA (tRNA) 修改对于理解蛋白质翻译和疾病至关重要.
- 由于修改密度高,检测tRNA修改具有挑战性.
- 纳米孔直接RNA测序为新的修改调用提供了新的可能性.
研究的目的:
- 用纳米孔测序绘制Schizosaccharomyces pombe中的伪尿素 (Ψ) 和其他tRNA修饰的图谱.
- 开发一种新的算法 (MoDorado),用于检测tRNA修改,超出初始模型训练中使用的.
- 扩大S. pombe. tRNA修饰的已知景观.
主要方法:
- 应用预先训练的纳米孔基调器模型 (Dorado) 在tRNA上检测伪尿素 (Ψ).
- 确定了已知的和新的 Ψ 位点及其相应的伪尿素合成酶.
- 开发并使用了MoDorado算法,通过比较已修改和未修改的样本来"非标签"检测多个tRNA修改.
主要成果:
- 在S. pombe.中绘制了已知并确定了两个新的伪乌里丁 (Ψ) 位点 (Ψ8和 Ψ22).
- 使用重新设计的模型,MoDorado成功检测到七个额外的tRNA修改 (ncm5U,mcm5U,mcm5s2U,m7G,queuosine,m1A和i6A).
- 在S. pombe.中生成了tRNA修饰的扩展地图.
结论:
- 纳米孔直接RNA测序与先进的算法相结合,可以实现全面的tRNA修饰概况.
- 莫多拉多为利用预训练模型发现新型RNA修饰提供了一个通用框架.
- 这项研究显著推进了tRNA修饰景观及其生物学影响的表征.
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