Adenovirus VAI RNA antagonizes the RNA-editing activity of the ADAR adenosine deaminase

Adenovirus VAI RNA antagonizes the RNA-editing activity of the ADAR adenosine deaminase
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DOI:
10.1006/viro.1998.9162
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发表时间:
1998-06-05
期刊:
影响因子:
3.7
通讯作者:
Samuel, CE
Samuel, CE
中科院分区:
医学3区
文献类型:
--
作者:
Lei, M;Liu, Y;Samuel, CE

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腺病毒的病毒相关VAI RNA是一种高度结构化的小RNA,其是在感染后晚期有效翻译细胞和病毒mRNA所需的。VAI RNA拮抗干扰素诱导的RNA依赖性蛋白激酶PKR的激活,PKR是翻译的重要调节因子。RNA特异性腺苷脱氨酶(阿达尔)是一种干扰素诱导的RNA编辑酶,可催化腺苷的位点选择性C-6脱氨作用,生成肌苷。阿达尔具有三个拷贝的高度保守的RNA结合基序(dsRBM),其类似于在PKR中发现的两个拷贝,PKR是发现原型dsRBM基序的酶。我们已经检查了VAI RNA对阿达尔功能的影响。VAI RNA损害阿达尔脱氨酶的活性。在用干扰素处理的人细胞和表达野生型重组阿达尔的猴COS细胞制备的提取物中可以观察到这种抑制作用。野生型和突变体形式的VA RNA的分析表明,中央结构域是重要的阿达尔活性的拮抗作用。这些结果表明,VAI RNA可能通过调节RNA编辑以及mRNA翻译来调节病毒和细胞基因表达。(C)北京:科学出版社.
The virus-associated VAI RNA of adenovirus is a small highly structured RNA that is required for the efficient translation of cellular and viral mRNAs at late times after infection. VAI RNA antagonizes the activation of the interferon-inducible RNA-dependent protein kinase, PKR, an important regulator of translation. The RNA-specific adenosine deaminase, ADAR, is an interferon-inducible RNA-editing enzyme that catalyzes the site-selective C-6 deamination of adenosine to inosine. ADAR possesses three copies of the highly conserved RNA-binding motif (dsRBM) that are similar to the two copies found in PKR, the enzyme in which the prototype dsRBM motif was discovered. We have examined the effect of VAI RNA on ADAR function. VAI RNA impairs the activity of ADAR deaminase. This inhibition can be observed in extracts prepared from interferon-treated human cells and from monkey COS cells in which wild-type recombinant ADAR was expressed. Analysis of wild-type and mutant forms of VA RNA suggests that the central domain is important in the antagonism of ADAR activity. These results suggest that VAI RNA may modulate viral and cellular gene expression by modulating RNA editing as well as mRNA translation. (C) 1998 Academic Press.