靶向RNA的CRISPR-Cas系统研究进展

Advances in the RNA-targeting CRISPR-Cas systems

摘要:

CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR associated proteins)系统是细菌和古细菌抵抗噬菌体、质粒等外源遗传物质的一种适应性免疫系统，该系统利用一种特殊的RNA (CRISPR RNA, crRNA)指导的内切酶来切割与crRNA相互补的外源遗传物质，从而阻碍外源核酸的侵染。根据效应复合物组成形式的不同，CRISPR-Cas系统分为1类(Ⅰ型、Ⅳ型和Ⅲ型)和2类(Ⅱ型、Ⅴ型和Ⅵ型)两大类。目前已发现多个CRISPR-Cas系统具有非常强的特异靶向RNA编辑能力，如Ⅵ型CRISPR-Cas13系统和Ⅲ型CRISPR-Cas7-11系统。随着研究的深入，相关系统在RNA编辑领域应用日渐广泛，使其成为基因编辑的有力工具。本文介绍了靶向RNA的CRISPR-Cas系统的组成、结构、分子机制以及其潜在应用，这为更好地研究该类系统的作用机制奠定基础，也为后期开发为稳定的基因编辑工具提供新的思路。

Abstract:

The CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR associated proteins) system is an adaptive immune system of bacteria and archaea against phages, plasmids and other exogenous genetic materials. The system uses a special RNA (CRISPR RNA, crRNA) guided endonuclease to cut the exogenous genetic materials complementary to crRNA, thus blocking the infection of exogenous nucleic acid. According to the composition of the effector complex, CRISPR-Cas system can be divided into two categories:class 1 (including type Ⅰ, Ⅳ, and Ⅲ) and class 2 (including type Ⅱ, Ⅴ, and Ⅵ). Several CRISPR-Cas systems have been found to have very strong ability to specifically target RNA editing, such as type Ⅵ CRISPR-Cas13 system and type Ⅲ CRISPR-Cas7-11 system. Recently, several systems have been widely used in the field of RNA editing, making them a powerful tool for gene editing. Understanding the composition, structure, molecular mechanism and potential application of RNA-targeting CRISPR-Cas systems will facilitate the mechanistic research of this system and provide new ideas for developing gene editing tools.