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调控CRISPR-Cas系统的机制。

Mechanisms regulating the CRISPR-Cas systems.

作者信息

Zakrzewska Marta, Burmistrz Michal

机构信息

Department of Environmental Microbiology and Biotechnology, Faculty of Biology, Institute of Microbiology, University of Warsaw, Warsaw, Poland.

Department of Molecular Microbiology, Biological and Chemical Research Centre, Faculty of Biology, University of Warsaw, Warsaw, Poland.

出版信息

Front Microbiol. 2023 Feb 28;14:1060337. doi: 10.3389/fmicb.2023.1060337. eCollection 2023.

Abstract

The CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeats- CRISPR associated proteins) is a prokaryotic system that enables sequence specific recognition and cleavage of nucleic acids. This is possible due to cooperation between CRISPR array which contains short fragments of DNA called spacers that are complimentary to the targeted nucleic acid and Cas proteins, which take part in processes of: acquisition of new spacers, processing them into their functional form as well as recognition and cleavage of targeted nucleic acids. The primary role of CRISPR-Cas systems is to provide their host with an adaptive and hereditary immunity against exogenous nucleic acids. This system is present in many variants in both Bacteria and Archea. Due to its modular structure, and programmability CRISPR-Cas system become attractive tool for modern molecular biology. Since their discovery and implementation, the CRISPR-Cas systems revolutionized areas of gene editing and regulation of gene expression. Although our knowledge on how CRISPR-Cas systems work has increased rapidly in recent years, there is still little information on how these systems are controlled and how they interact with other cellular mechanisms. Such regulation can be the result of both auto-regulatory mechanisms as well as exogenous proteins of phage origin. Better understanding of these interaction networks would be beneficial for optimization of current and development of new CRISPR-Cas-based tools. In this review we summarize current knowledge on the various molecular mechanisms that affect activity of CRISPR-Cas systems.

摘要

CRISPR-Cas(成簇规律间隔短回文重复序列- CRISPR相关蛋白)是一种原核生物系统,能够实现核酸的序列特异性识别和切割。这是由于CRISPR阵列(包含与靶向核酸互补的称为间隔序列的短DNA片段)与Cas蛋白之间的协同作用,Cas蛋白参与以下过程:获取新的间隔序列,将它们加工成功能形式以及识别和切割靶向核酸。CRISPR-Cas系统的主要作用是为其宿主提供针对外源核酸的适应性和遗传性免疫。该系统在细菌和古细菌中以多种变体形式存在。由于其模块化结构和可编程性,CRISPR-Cas系统成为现代分子生物学的一个有吸引力的工具。自发现和应用以来,CRISPR-Cas系统彻底改变了基因编辑和基因表达调控领域。尽管近年来我们对CRISPR-Cas系统工作方式的了解迅速增加,但关于这些系统如何被控制以及它们如何与其他细胞机制相互作用的信息仍然很少。这种调控可能是自我调节机制以及噬菌体来源的外源蛋白的结果。更好地理解这些相互作用网络将有利于优化当前基于CRISPR-Cas的工具并开发新工具。在本综述中,我们总结了目前关于影响CRISPR-Cas系统活性的各种分子机制的知识。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/585f/10013973/e44c415dc4be/fmicb-14-1060337-g001.jpg

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