在这项工作中,小组报告了在其天然宿主李斯特菌seeligeri中发现的抑制RNA靶向CRISPR-Cas13系统的rAcrVIA1 -一种质粒编码的小RNA。研究小组解决了Cas13-rAcr复合体的低温电镜结构,结果显示,尽管具有微不足道的序列相似性,但rAcrVIA1采用与crRNA几乎相同的折叠。总的来说,他们的发现扩大了rAcrs的多样性,并揭示了通过RNA结构模仿进行免疫拮抗的一个例子。
据悉,为了规避CRISPR-Cas免疫,噬菌体表达抑制Cas蛋白表达或活性的抗CRISPR因子。尽管迄今为止描述的大多数抗CRISPR是蛋白质,但最近描述的称为RNA抗CRISPR (rAcrs)的小RNA与CRISPR RNA (crRNAs)具有序列同源性,并将其从同源Cas核酸酶中取代。
附:英文原文
Title: RNA-mediated CRISPR-Cas13 inhibition through crRNA structural mimicry
Author: Victoria M. Hayes, Jun-Tao Zhang, Mark A. Katz, Yuelong Li, Benjamin Kocsis, David M. Brinkley, Ning Jia, Alexander J. Meeske
Issue&Volume: 2025-04-25
Abstract: To circumvent CRISPR-Cas immunity, phages express anti-CRISPR factors that inhibit the expression or activities of Cas proteins. Whereas most anti-CRISPRs described to date are proteins, recently described small RNAs called RNA anti-CRISPRs (rAcrs) have sequence homology to CRISPR RNAs (crRNAs) and displace them from cognate Cas nucleases. In this work, we report the discovery of rAcrVIA1—a plasmid-encoded small RNA that inhibits the RNA-targeting CRISPR-Cas13 system in its natural host, Listeria seeligeri. We solved the cryo–electron microscopy structure of the Cas13-rAcr complex, which revealed that rAcrVIA1 adopts a fold nearly identical to crRNA despite sharing negligible sequence similarity. Collectively, our findings expand the diversity of rAcrs and reveal an example of immune antagonism through RNA structural mimicry.
DOI: adr3656
Source: https://www.science.org/doi/10.1126/science.adr3656