加州大学Joseph Bondy-Denomy团队的最新研究提出了抗CRISPR触发的cas12 mRNA翻译依赖性降解。相关论文于2026年4月29日发表在《自然》杂志上。

在这里，该研究团队报告了一种意想不到的机制，通过抗CRISPR AcrVA2抑制Cas12a的生物发生。AcrVA2结合Cas12a N端附近的保守和功能重要的氨基酸残基，并在Cas12a mRNA被翻译时触发其选择性降解。此外，AcrVA2 C端结构域中的保守残基能够与核糖体和多体共同沉积，这是实现靶向共翻译mRNA降解所必需的。AcrVA2 C端结构域在由多种移动遗传元件编码的同源物中广泛保守，通常在缺乏Cas12a的宿主中，这表明这些同源物可能识别并下调其他细菌中的替代底物。这些发现揭示了细菌分子冲突和基因调控的新机制。

据介绍，细菌编码多种防御系统，包括CRISPR-Cas，以识别和切割噬菌体（噬菌体）和其他可移动遗传元件的DNA。作为回应，噬菌体编码抗CRISPR（Acr）蛋白，通过阻断DNA结合或切割来抑制CRISPR-Cas活性。

附：英文原文

Title: Translation-dependent degradation of cas12 mRNA triggered by an anti-CRISPR

Author: Marino, Nicole D., Talaie, Alexander, Gerovac, Milan, Rodriguez, Jorge L., Schmidt, Andrew D., Astmann, Theresa J., Carion, Hlose, Taylor, Anya Flood, Liliedahl, Jessica, Haniyur, Surabhi, Zoga, Kristi, Johnson, Matthew C., Buhlmann, Leandro, Chen, Kuei-Ho, Silas, Sukrit, Yuping, Li, Zhang, Yang, Swaney, Danielle L., Vogel, Jrg, Bondy-Denomy, Joseph

Issue&Volume: 2026-04-29

Abstract: Bacteria encode diverse defence systems, including CRISPR–Cas, to recognize and cleave the DNA of bacteriophages (phages) and other mobile genetic elements1. In response, phages encode anti-CRISPR (Acr) proteins that inhibit CRISPR–Cas activity by blocking DNA binding or cleavage2. Here we report an unexpected mechanism by which the anti-CRISPR AcrVA2 inhibits Cas12a biogenesis. AcrVA2 binds conserved and functionally important amino acid residues near the Cas12a N-terminus and triggers selective degradation of cas12a mRNA as it is translated. Additionally, conserved residues in the AcrVA2 C-terminal domain enable co-sedimentation with ribosomes and polysomes, which is required to achieve targeted co-translational mRNA degradation.  The AcrVA2 C-terminal domain is broadly conserved in homologs encoded by diverse mobile genetic elements, typically in hosts that lack cas12a, suggesting that these homologues may recognize and downregulate alternative substrates in other bacteria. These findings reveal a novel mechanism for molecular conflict and gene regulation in bacteria.

DOI: 10.1038/s41586-026-10440-8

Source: https://www.nature.com/articles/s41586-026-10440-8