针对第2大类CRISPR-Cas系统的acr基因的发现及Acr蛋白多样化的抑制机制

Discovery of acr genes for class 2 CRISPR-Cas systems and the distinct inhibition mechanisms of Acr proteins

CRISPR-Cas系统是细菌和古细菌来源的RNA介导的适应性免疫系统,利用RNA介导的核酸酶活性抵抗以噬菌体为代表的外源核酸的入侵.为逃避这种来源于宿主的免疫反应,噬菌体进化出了较小的anti-CRISPR蛋白(Acr).Acrs采用不同的抑制策略,将Cas效应蛋白限制在不同的阶段,从而使其失活.随着Cas蛋白在生物技术领域和临床上的广泛应用,Acr已被开发为有用的调控工具.对Acr的研究不仅可以加深人们对Cas蛋白别构调控的理解,而且可以为开发新型的基于Acr的调控工具打下基础.利用实验和生物信息学的手段,越来越多的Acr被发现,其中第2大类CRISPR-Cas系统目前有大约50种.本综述聚焦于第2大类CRISPR-Cas系统的Acr,从基因发现、抑制机制和技术应用三个方面对其进行总结,并对未来的研究方向做出展望.

CRISPR-Cas systems are adaptive immune systems from bacteria and archaea,which can defend the invasion of mobile genetic elements(MGEs)like bacteriophage through RNA-guided nuclease activities.To survive from immune systems from the host,phages have evolved anti-CRISPR proteins(Acrs)of relatively small size.Acrs employ versatile mechanisms to trap Cas proteins at various stages of action,thereby disabling their activities.As the widely applications of Cas proteins in biotechnological area and clinics,Acrs have been developed to useful regulation tools.The investigations on Acrs can not only deepen our understandings of the action mechanisms of Cas proteins,but also lay the foundation for engineering Acr-based regulation tools.Using experimental and bioinformatical methodologies,more and more Acrs are being discovered and characterized,nearly fifty of which are against Class 2 CRISPR-Cas systems currently.This paper focuses on these Acrs from Class 2 systems,summarizing them from the aspects of gene discovery,inhibition mechanisms and technical application,and providing prospectives for future studies.