Han Ju Hee, Lee So Yeon, Park Hyun Ho
College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea.
Department of Global Innovative Drugs, Graduate School of Chung-Ang University, Seoul, Republic of Korea.
FASEB J. 2025 Jun 30;39(12):e70753. doi: 10.1096/fj.202500684R.
The CRISPR-Cas system is a crucial adaptive immune mechanism in prokaryotes, providing defense against invading genetic elements. Among various CRISPR-Cas systems, the type VI-A system, employing RNA-guided RNase Cas13a, has been extensively studied for its ability to target and degrade single-stranded RNA. Anti-CRISPR (Acr) proteins have evolved as natural inhibitors of these systems, with AcrVIA proteins specifically targeting the Cas13a enzyme. However, there is currently conflicting debate regarding the anti-CRISPR function of AcrVIA6. This study reveals that AcrVIA6 functions as a DNA-binding protein rather than a Cas13a inhibitor, as it does not block RNA cleavage. These findings challenge its role in CRISPR-Cas regulation.
CRISPR-Cas系统是原核生物中一种关键的适应性免疫机制，可抵御入侵的遗传元件。在各种CRISPR-Cas系统中，利用RNA引导的核糖核酸酶Cas13a的VI-A型系统，因其靶向和降解单链RNA的能力而受到广泛研究。抗CRISPR（Acr）蛋白已进化成为这些系统的天然抑制剂，其中AcrVIA蛋白专门靶向Cas13a酶。然而，目前关于AcrVIA6的抗CRISPR功能存在相互矛盾的争论。这项研究表明，AcrVIA6作为一种DNA结合蛋白发挥作用，而不是Cas13a抑制剂，因为它不会阻断RNA切割。这些发现挑战了其在CRISPR-Cas调控中的作用。
