通过多个途径,RNA G-四复合体从一个紧的线圈状组合中出现
Pavlína Pokorná1,2, Vojtěch Mlýnský1, Jiří Šponer1
1Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, Brno 61200, Czech Republic.
Nucleic acids research
|September 9, 2025
概括
RNA G-四复合体 (rG4s) 对基因调节和稳定性至关重要. 它们复杂的折叠路径,涉及紧的线圈和短暂的二四结构,由分子动力学模拟揭示出来.
科学领域:
- 分子生物学分子生物学
- 生物物理学的生物物理.
- 遗传学 是一个遗传学.
背景情况:
- RNA G-四复合体 (rG4s) 是基因调节,翻译和基因组稳定的重要结构元素.
- 在mRNA未翻译区域中的rG4s会影响翻译效率和局部化.
- 长非编码RNA和端粒RNA中的rG4s与RNA处理和细胞衰老有关.
研究的目的:
- 为了阐明平行链RNA G-四重复的原子层折叠机制.
- 研究特定RNA序列的折叠路径,包括TERRA.
主要方法:
- 全原子增强采样分子动力学模拟.
- 温和的元动力学与溶解物温和相结合.
主要成果:
- RNA G-四重复折叠从一个紧的线圈组合开始,具有动态的关氨酸堆叠和配对.
- 三个四重奏rG4s的形成通过涉及重组的多种途径发生.
- 两个四重奏rG4结构作为共同的过渡合奏,表明一个复杂的,多路折叠过程.
结论:
- RNA G-四倍体折叠比以前预测的更复杂,没有明显的G-毛或G-三倍体中间体.
- 改进的采样方法对多维自由能量表面提出了挑战.
- 力量场的局限性被确定为模拟中的一个因素.
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