NAIL-MS显示tRNA和rRNA的低修饰是5-甲治疗的结果
Maximilian Berg1, Chengkang Li1, Stefanie Kaiser1
1Department of Pharmaceutical Chemistry, Goethe University Frankfurt, Frankfurt 60438, Germany.
Nucleic acids research
|February 25, 2025
概括
抗癌药物5-甲 (5-FU) 在转移RNA (tRNA) 和核糖体RNA (rRNA) 中引起广泛的RNA低基因改性. 这种RNA修饰缺陷是5-FU的潜在新机制.
科学领域:
- 分子生物学分子生物学
- 生物化学 生物化学
- 癌症研究 癌症研究
背景情况:
- 传统上已知抗癌药物5-fluorouracil (5-FU) 可以抑制甲基酸合成酶.
- 新出现的证据表明,5-FU毒性可能涉及核糖体碰撞和核糖体RNA (rRNA) 处理中的缺陷.
- 5-FU对RNA修饰的影响,特别是在转移RNA (tRNA) 和rRNA中,需要进一步研究.
研究的目的:
- 为了研究5-FU暴露对人体细胞中tRNA和rRNA修饰的影响.
- 阐明RNA低修饰在5-FU的作用机制中的作用.
主要方法:
- 用5-FU对待HEK293T细胞.
- 在tRNA和rRNA中的关键RNA修饰的量化.
- 核酸同位素标记与质谱学 (NAIL-MS) 结合使用,以区分先前存在的RNA与新合成的RNA的修改.
主要成果:
- 在tRNA中观察到5-甲基尤里丁和伪尤里丁 (Ψ) 修饰的显著减少 (55%和40%).
- 新合成的tRNA和rRNA显示了各种修饰的大量损失,包括 Ψ和核糖酶甲基化,而先前存在的RNA仍然被修饰.
- 在新转录的成熟rRNA中检测到成熟rRNA和低修饰水平的降低.
结论:
- 5-FU在tRNA和rRNA中都会诱导显著的RNA低调.
- 新合成的RNA特别容易受到5FU处理后的修饰缺陷的影响.
- RNA低基因改造代表了一种潜在的分子机制,有助于5-FU的抗癌活性.
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