The 3' to 5' Exoribonuclease DIS3: From Structure and Mechanisms to Biological Functions and Role in Human Disease.
The 3' to 5' Exoribonuclease DIS3: From Structure and Mechanisms to Biological Functions and Role in Human Disease.
复制标题
3'至5'驱虫核酸酶dis3：从结构和机制到生物学功能以及在人类疾病中的作用。
DOI：
10.3390/biom5031515
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发表时间：
2015-07-17
期刊：
影响因子：
5.5
通讯作者：
Newbury SF
中科院分区：
文献类型：
--
作者：
Robinson SR;Oliver AW;Chevassut TJ;Newbury SF
DIS 3是一种保守的核糖核酸外切酶和外泌体的催化亚基，是一种参与核和细胞质RNA种类的3'至5'降解和加工的蛋白质复合物。最近，DIS3的异常表达已被发现与一系列不同的癌症有关。也许最引人注目的是发现DIS3在11%的多发性骨髓瘤患者中复发突变。已经做了很多工作来阐明DIS3的结构和生化特征，包括其作为RNA衰变途径的效应子的作用的机制细节。然而，我们不知道DIS3突变如何导致癌症。有许多研究涉及DIS 3在生物体水平上的功能。S. pombe，S.酿酒酵母和果蝇表明DIS3同源物在细胞周期进程和微管组装中具有共同作用。DIS3最近还涉及小鼠B细胞的抗体多样化。本文旨在回顾DIS3的结构，机制和功能的现有知识，以及突出骨髓瘤患者中观察到的遗传模式，以深入了解DIS3突变在肿瘤发生中的假定作用。
DIS3 is a conserved exoribonuclease and catalytic subunit of the exosome, a protein complex involved in the 3' to 5' degradation and processing of both nuclear and cytoplasmic RNA species. Recently, aberrant expression of DIS3 has been found to be implicated in a range of different cancers. Perhaps most striking is the finding that DIS3 is recurrently mutated in 11% of multiple myeloma patients. Much work has been done to elucidate the structural and biochemical characteristics of DIS3, including the mechanistic details of its role as an effector of RNA decay pathways. Nevertheless, we do not understand how DIS3 mutations can lead to cancer. There are a number of studies that pertain to the function of DIS3 at the organismal level. Mutant phenotypes in S. pombe, S. cerevisiae and Drosophila suggest DIS3 homologues have a common role in cell-cycle progression and microtubule assembly. DIS3 has also recently been implicated in antibody diversification of mouse B-cells. This article aims to review current knowledge of the structure, mechanisms and functions of DIS3 as well as highlighting the genetic patterns observed within myeloma patients, in order to yield insight into the putative role of DIS3 mutations in oncogenesis.