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Molecular Mechanisms of RNA Targeting by Cas13-containing Type VI CRISPR-Cas Systems

机译：Cas13型VI型CAS系统RNA靶向的分子机制

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摘要

Prokaryotic adaptive immune systems use Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) and CRISPR-associated (Cas) proteins for RNA-guided cleavage of foreign genetic elements. The focus of this review, Type VI CRISPR-Cas systems, contain a single protein, Cas13 (formerly C2c2) that when assembled with a CRISPR-RNA (crRNA) forms a crRNA-guided RNA-targeting effector complex. Type VI CRISPR-Cas systems can be divided into four subtypes (A-D) based on Cas13 phylogeny. All Cas13 proteins studied to date possess two enzymatically distinct ribonuclease activities that are required for optimal interference. One RNase is responsible for pre-crRNA processing to form mature Type VI interference complexes, while the other RNase activity provided by the two Higher Eukaryotes and Prokaryotes Nucleotide-binding (HEPN) domains, is required for degradation of target-RNA during viral interference. In this review, I will compare and contrast what is known about the molecular architecture and behavior of Type VI (A-D) CRISPR Cas13 interference complexes, how this allows them to carry out their RNA-targeting function, how Type VI accessory proteins are able to modulate Cas13 activity, and how together all of these features have led to the rapid development of a range of RNA-targeting applications. Throughout I will also discuss some of the outstanding questions regarding Cas13's molecular behavior, and its role in bacterial adaptive immunity and RNA-targeting applications. (C) 2018 Elsevier Ltd. All rights reserved.
机译：原核自适应免疫系统使用聚类定期间隙的短语重复（CRISPRS）和CRISPR相关（CAS）蛋白的RNA引导的外来遗传元素的切割。本综述的重点，型VI CRISPR-CAS系统含有单一蛋白质，CAS13（以前的C2C2），当用CRISPR-RNA（CRRNA）形成CRRNA引导的RNA靶向效应复合物。类型VI CRISPR-CAS系统可分为基于Cas13 Phylogy的四种亚型（A-D）。研究迄今为止的所有CAS13蛋白质具有两种酶促性核糖核酸酶的最佳干扰所需的活动。一个RNase负责预cRRNA处理以形成成熟型VI干扰复合物，而在病毒干扰过程中，由两个较高的真核生物和原核苷酸核苷酸结合（HEPN）结构域提供的其他RNase活性。在本次审查中，我将比较和对比VI（AD）CRISPR CAS13干扰复合物的分子架构和行为所知的内容，这使其允许它们进行RNA靶向功能，VI型辅助蛋白类型如何调制CAS13活动，以及所有这些特征如何导致一系列RNA靶向应用的快速发展。在我曾经讨论了关于CAS13的分子行为的一些出色问题，以及其在细菌适应症免疫和RNA靶向应用中的作用。 （c）2018年elestvier有限公司保留所有权利。

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