据介绍，RNA引导的核糖核酸酶CRISPR-Cas13能够在细菌中实现适应性免疫，并在异源系统中实现可编程的RNA操纵。Cas13的序列相似性有限，阻碍了相关或祖先系统的发现。
为了解决这个问题，研究人员开发了一个自动结构搜索管道，以鉴定Cas13的祖先分支（Cas13an），并进一步追踪Cas13起源于防御相关的核糖核酸酶。尽管Cas13an的大小是其他Cas13的三分之一，但它介导了强大的可编程RNA耗竭和对多种噬菌体的防御。
然而，与较大的对应物不同，Cas13an使用单个活性位点进行CRISPR RNA加工和RNA引导切割，揭示了祖先核酸酶结构域有两种活性模式。Cas13an的发现深化了人们对CRISPR-Cas演化的理解，扩大了精确RNA编辑的机会，展示了结构导向基因组挖掘的前景。
附：英文原文
Title: Structure-guided discovery of ancestral CRISPR-Cas13 ribonucleases
Author: Peter H. Yoon, Zeyuan Zhang, Kenneth J. Loi, Benjamin A. Adler, Arushi Lahiri, Kamakshi Vohra, Honglue Shi, Daniel Bellieny Rabelo, Marena Trinidad, Ron S. Boger, Muntathar J. Al-Shimary, Jennifer A. Doudna
Issue&Volume: 2024-07-18
Abstract: The RNA-guided ribonuclease CRISPR-Cas13 enables adaptive immunity in bacteria and programmable RNA manipulation in heterologous systems. Cas13s share limited sequence similarity, hindering discovery of related or ancestral systems. To address this, we developed an automated structural-search pipeline to identify an ancestral clade of Cas13 (Cas13an), and further trace Cas13 origins to defense-associated ribonucleases. Despite being one third the size of other Cas13s, Cas13an mediates robust programmable RNA depletion and defense against diverse bacteriophages. However, unlike its larger counterparts, Cas13an uses a single active site for both CRISPR RNA processing and RNA-guided cleavage, revealing the ancestral nuclease domain has two modes of activity. Discovery of Cas13an deepens our understanding of CRISPR-Cas evolution and expands opportunities for precision RNA editing, showcasing the promise of structure-guided genome mining.
DOI: adq0553
Source: https://www.science.org/doi/10.1126/science.adq0553