循环 permuted II 组内自拼接的结构基础.
Liu Wang1,2, Jiahao Xie1,3, Chong Zhang1
1The State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital; The State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, National Center for Stomatology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Nature structural & molecular biology
|January 31, 2025
概括
循环 permuted II 组内子 (CP 内子) 通过一个独特的反拼接机制产生循环RNA. 冷电磁结构揭示了对这一过程至关重要的域重组和金属离子稳定,推进了circRNA研究.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 在RNA生物学,RNA生物学.
背景情况:
- 循环RNAs (circRNAs) 越来越多地被认为是它们的调节作用.
- 循环 permuted II 组内基子 (CP 内基子) 的circRNAs的生物发生尚未得到充分理解.
- CP 内子具有重新排列的结构域和绑定的外子,导致分支的内子和圆形外子.
研究的目的:
- 阐明由CP内核生成circRNA的结构和机制基础.
- 以高分辨率来解决CP内核中的反拼接的动态过程.
- 识别 CP 内子拼接中涉及的独特结构特征和分子相互作用.
主要方法:
- 电子显微镜 (cryo-EM) 用于确定高分辨率结构 (2.5-2.9 Å).
- 在多个功能状态下对自然的CP内子进行分析.
- 进行比较基因组学以识别和分析额外的CP内核.
主要成果:
- 详细的冷EM结构揭示了6域的形状变化,促进了3'-外显子的识别和循环化.
- 观察到前所未有的三级相互作用,将催化三元和域6压缩为蛋白质独立拼接.
- 确定了一种特定的金属离子 (M35) 在剪接反应期间稳定5'-外接子.
- 这些独特的特征,不同于正规II组内基子,在其他CP内基子中保留.
结论:
- 这项研究阐明了CP内逆拼接的动态机制,揭示了circRNA形成的关键结构适应.
- 研究结果提供了关于 CP 内子独特的催化策略的关键见解.
- 这些结果对理解circRNA生物发生和开发基于circRNA的新疗法具有重大意义.
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