RNA-mediated CRISPR-Cas13 inhibition through crRNA structural mimicry

IF 44.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Pub Date : 2025-04-24 DOI:10.1126/science.adr3656

Victoria M. Hayes, Jun-Tao Zhang, Mark A. Katz, Yuelong Li, Benjamin Kocsis, David M. Brinkley, Ning Jia, Alexander J. Meeske

引用次数: 0

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.

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通过crRNA结构模拟介导的CRISPR-Cas13抑制

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 （crrna）具有序列同源性，并将其从同源Cas核酸酶中取代。在这项工作中，我们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。我们解决了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，我们的发现扩大了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。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

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