2025年2月18日，美国麻省理工学院和哈佛大学的张锋小组在《细胞》杂志发表论文，宣布他们发现了靶向重编程RNA的CRISPR系统是从RNA毒素抗毒素进化而来的。
小组描述了一种集成的序列/结构进化追踪方法来识别RNA靶向CRISPR-Cas13系统的祖先。研究人员发现Cas13可能是从AbiF进化而来的，AbiF是由一个与保守的非编码RNA （ncRNA）稳定相关的流产感染相关基因编码的。研究团队进一步表征了一种微型Cas13，在这里被分类为Cas13e，它作为AbiF和其他已知Cas13s之间的进化中间体。尽管存在这种关系，但该课题组表明它们的功能有很大的不同。Cas13e是一种RNA引导的RNA靶向系统，而AbiF是一种含有RNA抗毒素的毒素-抗毒素（TA）系统。
该研究组解决了AbiF主题冷冻电子显微镜（cro - EM）的结构，揭示了将Cas13s与AbiF区分开来的基本结构变化。最后，研究团队绘制了关键的结构变化，使非引导的TA系统演变成rna引导的CRISPR系统。
据悉，尽管人们一直在努力研究CRISPR系统，但对重编程RNA引导机制的进化起源仍然知之甚少。
附：英文原文
Title: Reprogrammable RNA-targeting CRISPR systems evolved from RNA toxin-antitoxins
Author: Shai Zilberzwige-Tal, Han Altae-Tran, Soumya Kannan, Max E. Wilkinson, Samuel Chau-Duy-Tam Vo, Daniel Strebinger, KeHuan K. Edmonds, Chun-Chen Jerry Yao, Kepler S. Mears, Sergey A. Shmakov, Kira S. Makarova, Rhiannon K. Macrae, Eugene V. Koonin, Feng Zhang
Issue&Volume: 2025-02-18
Abstract: Despite ongoing efforts to study CRISPR systems, the evolutionary origins giving rise to reprogrammable RNA-guided mechanisms remain poorly understood. Here, we describe an integrated sequence/structure evolutionary tracing approach to identify the ancestors of the RNA-targeting CRISPR-Cas13 system. We find that Cas13 likely evolved from AbiF, which is encoded by an abortive infection-linked gene that is stably associated with a conserved non-coding RNA (ncRNA). We further characterize a miniature Cas13, classified here as Cas13e, which serves as an evolutionary intermediate between AbiF and other known Cas13s. Despite this relationship, we show that their functions substantially differ. Whereas Cas13e is an RNA-guided RNA-targeting system, AbiF is a toxin-antitoxin (TA) system with an RNA antitoxin. We solve the structure of AbiF using cryoelectron microscopy (cryo-EM), revealing basic structural alterations that set Cas13s apart from AbiF. Finally, we map the key structural changes that enabled a non-guided TA system to evolve into an RNA-guided CRISPR system.
DOI: 10.1016/j.cell.2025.01.034
Source: https://www.cell.com/cell/abstract/S0092-8674(25)00103-5