XRN 5'→3' exoribonucleases: structure, mechanisms and functions.

XRN 5'→3' exoribonucleases: structure, mechanisms and functions.
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XRN 5'→3'驱虫核酸酶:结构,机制和功能。

DOI:
10.1016/j.bbagrm.2013.03.005
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发表时间:
2013-06
影响因子:
4.7
通讯作者:
Green, Pamela J.
Green, Pamela J.
中科院分区:
生物学2区
文献类型:
--
作者:
Nagarajan, Vinay K.;Jones, Christopher I.;Newbury, Sarah F.;Green, Pamela J.

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XRN家族的5‘→3’外切核糖核酸酶对于确保真核生物细胞内核糖核酸周转的保真度是至关重要的。该家族在物种间高度保守,通常由一个细胞质酶(XRN1/Pacman或XRN4)和一个或多个核酶(XRN2/RAT1和XRN3)代表。细胞质和/或核XRN已被证明在所有被测试的生物体中是必不可少的,缺陷可能具有严重的发育表型,表明XRN在真菌、植物和动物中是不可或缺的。XRN在一般的RNA衰变过程中降解不同的RNA底物,并在RNA代谢所必需的特殊过程中发挥作用,如无义介导的衰变(NMD)、基因沉默、rRNA成熟和转录终止。在这里,我们回顾了XRN的现有知识,强调了最近的高影响和未来潜力的工作。一个例子是我们对XRN1如何连续降解5‘单磷酸化RNA的理解取得了突破,通过晶体结构和突变分析揭示了这一点。概述了XRN底物和相互作用伙伴的扩展知识,并利用现有的突变表型在生物体水平上解释了XRN的功能。最后,更详细地讨论了三个案例研究,以强调XRN功能的几个最令人兴奋的研究领域:XRN4参与植物中的小RNA相关过程,XRN1/Pacman在果蝇发育中的作用,以及人类XRN2在核转录质量控制中的功能。这篇文章是题为:RNA衰变机制的特刊的一部分。
The XRN family of 5’→3’ exoribonucleases is critical for ensuring the fidelity of cellular RNA turnover in eukaryotes. Highly conserved across species, the family is typically represented by one cytoplasmic enzyme (XRN1/PACMAN or XRN4) and one or more nuclear enzymes (XRN2/RAT1 and XRN3). Cytoplasmic and/or nuclear XRNs have proven to be essential in all organisms tested, and deficiencies can have severe developmental phenotypes, demonstrating that XRNs are indispensable in fungi, plants and animals. XRNs degrade diverse RNA substrates during general RNA decay and function in specialized processes integral to RNA metabolism, such as nonsense-mediated decay (NMD), gene silencing, rRNA maturation, and transcription termination. Here, we review current knowledge of XRNs, highlighting recent work of high impact and future potential. One example is the breakthrough in our understanding of how XRN1 processively degrades 5’ monophosphorylated RNA, revealed by its crystal structure and mutational analysis. The expanding knowledge of XRN substrates and interacting partners is outlined and the functions of XRNs are interpreted at the organismal level using available mutant phenotypes. Finally, three case studies are discussed in more detail to underscore a few of the most exciting areas of research on XRN function: XRN4 involvement in small RNA-associated processes in plants, the roles of XRN1/PACMAN in Drosophila development, and the function of human XRN2 in nuclear transcriptional quality control. This article is part of a Special Issue entitled: RNA Decay Mechanisms.
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