Mov10蛋白生物学功能研究进展

[摘要] Mov10 蛋白属于RNA 解旋酶超家族—1,是 RNA—诱导沉默复合体的组成成分之一。

Mov10 蛋白在介导miRNA/siRNA基因沉默中有积极的作用,其确切机制尚不清楚。

研究证实,Mov10 蛋白具有广泛和有效的抗逆转录病毒活性,能在多阶段抑制HIV—1复制,包括病毒产生、Gag 蛋白水解程序、逆转录过程;同时也可降低其他逆转录病毒如猿类免疫缺陷病毒、鼠白血病病毒和马传染性贫血病毒的感染性。

新近研究发现Mov10在肿瘤中表达升高,推测其与hTERT和端粒相关,参与肿瘤的形成和肿瘤细胞的分化。

毕业论文网 /6/view—11642200.htm  [关键词] Mov10蛋白;RNA解旋酶生物学功能;RNA干扰   [中图分类号] R34 [文献标识码] A [文章编号] 1673—9701(2015)23—0157—04   Research progress of biological function on Mov10 protein   LIU Minhui1 SHENG Yunjian2 FU Yuejuan1 CHEN Haijun1 REN Hong3 TANG Hui3   1.Department of Infectious Diseases, Jinhua Municipal Central Hospital, Jinhua 321000,China; 2.Department of Infectious Diseases, the Affiliated Hospital of Luzhou Medical College, Luzhou 646000,China; 3.Institute of Viral Hepatitis, Chongqing Medical University, Chongqing 400010, China   [Abstract] Mov10 protein is a member of RNA helicase—1 superfamily, and it is also one of the components of the RNA—induced silencing complex. Mov10 plays an important role in miRNA/siRNA—induced gene silencing, but the exact mechanism remains unknown. Studies have show that Mov10 protein widely and potently inhibits HIV—1 replication at multiple stages, including virus production, proteolytic processing of Gag, and reverse transcription. Meanwhile, Mov10 can reduce the infectivity of other retrovirus such as simian immunodeficiency virus, murine leukemia virus and equine infectious anemia virus. Recent research described that Mov10 overexpressed in tumors and speculated to involve carcinogenesis and differentiation relating to hTERT and telomere.   [Key words] Mov10 protein; RNA helicase; Biological function; RNA interference   莫罗尼白血病病毒10(Moloney leukemia virus 10,Mov10)蛋白是新发现的一种具有广谱抗逆转录病毒潜能的因子。

Mov10蛋白属于RNA解旋酶超家族—1(SF—1)[1,2],是RNA—诱导沉默复合体(RISC)的组成成分[3,4]。

近年Mov10相关研究主要集中于其在RNA干扰(RNAi)过程中的功能及其对HIV—1等逆转录病毒复制的抑制及其机制[5—7];此外,MOV10尚能降低其他逆转录病毒,如猿类免疫缺陷病病毒、鼠白血病病毒、马传染性贫血病毒等的感染性[7—9]。

本文就Mov10蛋白生物学功能的新进研究进展进行综述。

1 Mov10蛋白的发现   MOV10基因首先发现于Mov10小鼠品系,Mov鼠系是通过用鼠莫罗尼白血病病毒(Moloney murine leukemia virus,M—MuLV)感染早期胚胎而获得,根据单拷贝前病毒发生整合的不同染色体位点,分为9个种系,将其命名为Mov5~Mov13。

其中只有Mov10鼠系未发生病毒血症,这表明其体内前病毒无活性[10]。

后来发现,前病毒已整合至一个进化保守基因位点,后将其命名为Mov10基因

随后Meister G等[11]在研究RISC时纯化含Ago的复合物,首次分离出大小为130 KDa的新蛋白,经测序分析将其将鉴定为Mov10蛋白,此研究提出Mov10与人Ago1和Ago2相关,共同结合于RISC。

2 MOV10基因蛋白结构和组织分布   解旋酶一般含7个保守序列(Ⅰ,Ia,Ⅱ,Ⅲ,Ⅳ,Ⅴ和Ⅵ),分为SF—1、SF—2和SF—3三个超家族,另外还有F4和F5两个小家族[12,13]。

人类MOV10基因位于1号染色体1p13.2,编码含1003个氨基酸的Mov10蛋白

Mov10蛋白含7个解旋酶基序,具有DEAG指纹结构,因此被归为SF—1[14]。

近期研究报道,Mov10类似于Upf1解旋酶组,能在多个步骤抑制HIV—1复制[7];最新研究进一步显示,Mov10与Upf1紧密结合于mRNA3’端UTRS上游区域,使mRNA局部形成二级结构,介导无意义mRNA降解[15]。

不同物种间Mov10蛋白序列具有较好的保守性,人与恒河猴、小鼠间Mov10蛋白的相似度分别达99%和91%。

Mov10蛋白在进化过程中的高度保守性表明其在生物个体发育中起重要作用[5]。

4 结语   综上所述,虽然Mov10蛋白生物学功能尚未完全明确,但其在RNA干扰路径中的重要作用及广谱抗逆转录病毒活性的功能不可否认。

近年来,Mov10蛋白基因沉默及抗逆转录病毒作用的相关研究继续深入,而在肿瘤、高血压等疾病方面的研究也初露端倪。

因此,对Mov10蛋白生物学功能更深入的了解将为开发更有效的抗逆转录病毒感染治疗方法提供新策略,也为研究者认识Mov10蛋白对其他疾病的影响提供了新观点。

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