Murine APOBEC1 Is a Powerful Mutator of Retroviral and Cellular RNA In Vitro and In Vivo
Murine APOBEC1 Is a Powerful Mutator of Retroviral and Cellular RNA In Vitro and In Vivo
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DOI：
10.1016/j.jmb.2008.10.043
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发表时间：
2009-01-09
影响因子：
5.6
通讯作者：
Vartanian, Jean-Pierre
中科院分区：
文献类型：
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作者：
Petit, Vincent;Guetard, Denise;Vartanian, Jean-Pierre
哺乳动物的载脂蛋白B mRNA编辑酶催化多肽样（APOBEC）分子包含一大类胞苷脱氨酶，对RNA和单链DNA（ssDNA）具有特异性。APOBEC1总是具有高度特异性，能编辑细胞mRNA中的一个单一残基，而APOBEC3在细胞中的作用靶点尚未明确，尽管它们可能抑制某些反转录转座子的转座。人类APOBEC3的七种酶中的两种在体外和体内都强烈限制人类免疫缺陷病毒I型。我们在此表明，在体外，小鼠APOBEC1和APOBEC3脱氨酶对一种感染性外源性γ逆转录病毒——弗氏鼠白血病病毒的ssDNA进行了过度编辑。小鼠APOBEC1也能够使鼠白血病病毒基因组RNA中的胞苷残基过度脱氨。对编辑位点的分析表明，体内的脱氨是由小鼠APOBEC1而非APOBEC3引起的。此外，小鼠APOBEC1能够在体内对其主要底物——载脂蛋白B mRNA以及多种异源RNA进行过度编辑。简而言之，小鼠APOBEC1在体内是RNA和ssDNA的超突变剂，过度表达时可能会产生偶尔的副作用。（C）2008爱思唯尔有限公司。保留所有权利。
Mammalian APOBEC molecules comprise a large family of cytidine deaminases with specificity for RNA and single-stranded DNA (ssDNA). APOBEC1s are invariably highly specific and edit a single residue in a cellular mRNA, while the cellular targets for APOBEC3s are not clearly established, although they may curtail the transposition of some retro-transposons. Two of the seven member human APOBEC3 enzymes strongly restrict human immunodeficiency virus type I in vitro and in vivo. We show here that ssDNA hyperediting of an infectious exogenous gammaretrovirus, the Friend-murine leukemia virus, by murine APOBEC1 and APOBEC3 deaminases occurs in vitro. Murine APOBEC1 was able to hyperdeaminate cytidine residues in murine leukemia virus genomic RNA as well. Analysis of the edited sites shows that the dearnination in vivo was due to mouse APOBEC1 rather than APOBEC3. Furthermore, murine APOBEC1 is able to hyperedit its primary substrate in vivo, the apolipoprotein B mRNA, and a variety of heterologous RNAs. In short, murine APOBEC1 is a hypermutator of both RNA and ssDNA in vivo, which could exert occasional side effects upon overexpression. (C) 2008 Elsevier Ltd. All rights resented.