一种可编程的核糖酶用于RNA信号传导.
Mandy Yu Theng Lim1, Chermaine Tan1, Charannya Sozheesvari Subhramanyam1
1Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
Nature communications
|January 10, 2026
概括
研究人员开发了一种新的RNA系统 (UNLOCKED by Activating RNA - UNBAR),可以检测特定的RNA序列并触发功能输出. 这种可编程平台可以实现基于RNA的传感和高特异性的基因调节.
科学领域:
- 合成生物学 合成生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 对于各种应用来说,RNA检测至关重要,但对感知RNA的直接功能转导仍然是一个挑战.
- 现有的方法缺乏一种可通用的方法来将RNA触发器与各种非编码RNA效应器联系起来.
研究的目的:
- 设计一种可编程RNA激活系统,用于直接功能转导RNA触发器.
- 开发一种用于RNA传感,放大和效应器释放的多功能平台.
主要方法:
- 在单个RNA链中编码的双站点自切割的 ribozyme 平台 (未通过激活RNA锁定 - UNBAR) 的工程.
- 为单核酸触发特异性和模块性设计UNBAR核酶.
- 展示无细胞和细胞内应用,包括微RNA和病毒RNA检测,以及CRISPR-Cas9基因编辑调节.
主要成果:
- 没有触发剂的UNBAR ribozymes具有很高的不活性和单核酸特异性.
- 该系统可实现无蛋白放大和触发器依赖释放非编码RNA效应器 (sgRNA,shRNA,aptamer).
- 在斑马鱼和人类细胞中,通过切割的阿帕特马来进行直接光读取和触发依赖的CRISPR-Cas9编辑,证明了功能转导.
结论:
- UNBAR代表了一流的RNA激活系统,用于直接的功能转导.
- 这种可编程平台对合成生物学,诊断和基因调节应用具有重大潜力.
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