a Department of Chemistry and Biochemistry, Alberta RNA Research and Training Institute , University of Lethbridge , Lethbridge , Canada.
b Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine , University of Calgary , Calgary , Canada.
Biotechnol Genet Eng Rev. 2018 Apr;34(1):3-32. doi: 10.1080/02648725.2018.1467146. Epub 2018 May 9.
Viruses hijack the host cell machinery and recruit host proteins to aid their replication. Several host proteins also play vital roles in inhibiting viral replication. Emerging class of host proteins central to both of these processes are the DEAD-box helicases: a highly conserved family of ATP-dependent RNA helicases, bearing a common D-E-A-D (Asp-Glu-Ala-Asp) motif. They play key roles in numerous cellular processes, including transcription, splicing, miRNA biogenesis and translation. Though their sequences are highly conserved, these helicases have quite diverse roles in the cell. Interestingly, often these helicases display contradictory actions in terms of the support and/or clearance of invading viruses. Increasing evidence highlights the importance of these enzymes, however, little is known about the structural basis of viral RNA recognition by the members of the DEAD-box family. This review summarizes the current knowledge in the field for selected DEAD-box helicases and highlights their diverse actions upon viral invasion of the host cell. We anticipate that through a better understanding of how these helicases are being utilized by viral RNAs and proteins to aid viral replication, it will be possible to address the urgent need to develop novel therapeutic approaches to combat viral infections.
病毒劫持宿主细胞机制,并招募宿主蛋白来帮助其复制。一些宿主蛋白在抑制病毒复制方面也起着至关重要的作用。新兴的一类在这两个过程中都起核心作用的宿主蛋白是 DEAD-box 解旋酶:一种高度保守的 ATP 依赖的 RNA 解旋酶家族,具有共同的 D-E-A-D(天冬氨酸-谷氨酸-丙氨酸-天冬氨酸)基序。它们在许多细胞过程中发挥关键作用,包括转录、剪接、miRNA 生物发生和翻译。尽管它们的序列高度保守,但这些解旋酶在细胞中的作用却非常多样化。有趣的是,这些解旋酶通常在支持和/或清除入侵病毒方面表现出矛盾的作用。越来越多的证据强调了这些酶的重要性,然而,对于 DEAD-box 家族成员识别病毒 RNA 的结构基础知之甚少。这篇综述总结了选定的 DEAD-box 解旋酶在该领域的最新知识,并强调了它们在宿主细胞受到病毒入侵时的多样化作用。我们预计,通过更好地了解病毒 RNA 和蛋白如何利用这些解旋酶来辅助病毒复制,就有可能满足开发新型治疗方法以对抗病毒感染的迫切需求。