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双链 RNA 激活的 ATP 酶 (DRAs):RNA 感应、信号转导和加工的平台。

Duplex RNA activated ATPases (DRAs): platforms for RNA sensing, signaling and processing.

机构信息

Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT, USA.

出版信息

RNA Biol. 2013 Jan;10(1):111-20. doi: 10.4161/rna.22706. Epub 2012 Dec 10.

Abstract

Double-stranded RNAs are an important class of functional macromolecules in living systems. They are usually found as part of highly specialized intracellular machines that control diverse cellular events, ranging from virus replication, antiviral defense, RNA interference, to regulation of gene activities and genomic integrity. Within different intracellular machines, the RNA duplex is often found in association with specific RNA-dependent ATPases, including Dicer, RIG-I and DRH-3 proteins. These duplex RNA-activated ATPases represent an emerging group of motor proteins within the large and diverse super family 2 nucleic acid-dependent ATPases (which are historically defined as SF2 helicases). The duplex RNA-activated ATPases share characteristic molecular features for duplex RNA recognition, including motifs (e.g., motifs IIa and Vc) and an insertion domain (HEL2i), and they require double-strand RNA binding for their enzymatic activities. Proteins in this family undergo large conformational changes concomitant with RNA binding, ATP binding and ATP hydrolysis in order to achieve their functions, which include the release of signaling domains and the recruitment of partner proteins. The duplex RNA-activated ATPases represent a distinct and fascinating group of nanomechanical molecular motors that are essential for duplex RNA sensing and processing in diverse cellular pathways.

摘要

双链 RNA 是活细胞中一类重要的功能大分子。它们通常作为高度专业化的细胞内机器的一部分存在,这些机器控制着从病毒复制、抗病毒防御、RNA 干扰到基因活性和基因组完整性调节等各种细胞事件。在不同的细胞内机器中,双链 RNA 常与特定的 RNA 依赖性 ATP 酶(如 Dicer、RIG-I 和 DRH-3 蛋白)结合。这些双链 RNA 激活的 ATP 酶代表了大型和多样化的 2 型核酸依赖性 ATP 酶(历史上被定义为 SF2 解旋酶)超级家族中的一个新兴的马达蛋白群。双链 RNA 激活的 ATP 酶具有双链 RNA 识别的特征分子特征,包括基序(例如,基序 IIa 和 Vc)和插入结构域(HEL2i),并且它们的酶活性需要双链 RNA 结合。该家族中的蛋白质在与 RNA 结合、ATP 结合和 ATP 水解的同时发生大的构象变化,以实现其功能,包括信号域的释放和伴侣蛋白的募集。双链 RNA 激活的 ATP 酶代表了一类独特而迷人的纳米机械分子马达,它们对于双链 RNA 在各种细胞途径中的感应和加工至关重要。

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