全球RNA对MALAT1三重螺旋的修改对热稳定性产生差异性影响,并削弱与METTL16的结合
Mika J Schievelbein1, Carlos Resende1, Madeline M Glennon1
1Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA.
The Journal of biological chemistry
|December 13, 2023
概括
像N6-甲基氨酸 (m6A) 和伪氨酸 (Ψ) 这样的RNA修饰改变RNA结构和蛋白质结合. 治疗mRNA中的这些化学变化会影响免疫规避和功能.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 在RNA治疗方面,RNA疗法.
背景情况:
- 治疗性信使RNAs (mRNAs) 使用修饰的核酸,如N1-methylpseudouridine (m1Ψ),以逃避免疫检测.
- 全球RNA修饰对RNA结构和功能的影响仍然不完全理解.
研究的目的:
- 研究全球RNA修饰如何影响转移相关的肺腺癌转录1 (MALAT1) 三重螺旋体的结构和蛋白质结合.
- 阐明N6-甲基氨酸 (m6A),伪尿素 (Ψ) 和m1Ψ在调节RNA稳定性和蛋白质相互作用中的作用.
主要方法:
- 紫外线热变质试验用于评估RNA的结构稳定性.
- 原生凝转移测试以评估RNA-蛋白质结合亲和力.
主要成果:
- m6A使RNA结构不稳定了~20°C,而 Ψ和m1Ψ使稳定性分别增加了~12°C和~9°C.
- 使用m6A, Ψ和m1Ψ的RNA修改使甲基转移酶样蛋白16 (METTL16) 的结合分别减弱了8,99和23倍.
- 增加的RNA热稳定性与增强的RNA-蛋白相互作用没有相关性.
结论:
- RNA的修改显著影响RNA结构和蛋白质结合,独立于热稳定性.
- 这些发现凸显了RNA修饰在生物过程和治疗应用中的多方面的调节作用.
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