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DEAD-box RNA 解旋酶:病毒复制与抗病毒先天免疫交叉路口处 RNA 代谢的驱动力。

DEAD-box RNA helicases: The driving forces behind RNA metabolism at the crossroad of viral replication and antiviral innate immunity.

机构信息

Department of Biochemistry, Faculty of Science, Ain Shams University, Abbassia, 11566, Cairo, Egypt.

出版信息

Virus Res. 2021 Apr 15;296:198352. doi: 10.1016/j.virusres.2021.198352. Epub 2021 Feb 25.

DOI:10.1016/j.virusres.2021.198352
PMID:33640359
Abstract

DEAD-box RNA helicases, the largest family of superfamily 2 helicases, are a profoundly conserved family of RNA-binding proteins, containing a distinctive Asp-Glu-Ala-Asp (D-E-A-D) sequence motif, which is the origin of their name. Aside from the ATP-dependent unwinding of RNA duplexes, which set up these proteins as RNA helicases, DEAD-box proteins have been found to additionally stimulate RNA duplex fashioning and to uproot proteins from RNA, aiding the reformation of RNA and RNA-protein complexes. There is accumulating evidence that DEAD-box helicases play functions in the recognition of foreign nucleic acids and the modification of viral infection. As intracellular parasites, viruses must avoid identification by innate immune sensing mechanisms and disintegration by cellular machinery, whilst additionally exploiting host cell activities to assist replication. The capability of DEAD-box helicases to sense RNA in a sequence-independent way, as well as the broadness of cellular roles performed by members of this family, drive them to affect innate sensing and viral infections in numerous manners. Undoubtedly, DEAD-box helicases have been demonstrated to contribute to intracellular immune recognition, function as antiviral effectors, and even to be exploited by viruses to support their replication. Relying on the virus or the viral cycle phase, a DEAD-box helicase can function either in a proviral manner or as an antiviral factor. This review gives a comprehensive perspective on the various biochemical characteristics of DEAD-box helicases and their links to structural data. It additionally outlines the multiple functions that members of the DEAD-box helicase family play during viral infections.

摘要

DEAD-box RNA 解旋酶是超家族 2 解旋酶中最大的家族,是一类高度保守的 RNA 结合蛋白家族,含有独特的 Asp-Glu-Ala-Asp (D-E-A-D) 序列基序,这也是它们名称的由来。除了依赖于 ATP 的 RNA 双链解旋外,这些蛋白还被发现可以额外地刺激 RNA 双链的形成,并将蛋白质从 RNA 上逐出,从而帮助 RNA 的重新形成和 RNA-蛋白质复合物的重构。越来越多的证据表明,DEAD-box 解旋酶在识别外来核酸和修饰病毒感染方面发挥作用。作为细胞内寄生虫,病毒必须避免被先天免疫感应机制识别,并被细胞机制破坏,同时还利用宿主细胞的活动来协助复制。DEAD-box 解旋酶能够以非序列依赖的方式感知 RNA,以及该家族成员所执行的广泛的细胞功能,促使它们以多种方式影响先天感应和病毒感染。毫无疑问,DEAD-box 解旋酶已被证明有助于细胞内免疫识别,作为抗病毒效应因子,甚至被病毒利用来支持其复制。依赖于病毒或病毒周期阶段,DEAD-box 解旋酶可以以促进病毒的方式或作为抗病毒因子发挥作用。这篇综述全面介绍了 DEAD-box 解旋酶的各种生化特性及其与结构数据的联系。它还概述了 DEAD-box 解旋酶家族成员在病毒感染过程中发挥的多种功能。

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