Intrinsic restriction activity by apolipoprotein B mRNA editing enzyme APOBEC1 against the mobility of autonomous retrotransposons.

Intrinsic restriction activity by apolipoprotein B mRNA editing enzyme APOBEC1 against the mobility of autonomous retrotransposons.
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DOI:
10.1093/nar/gkr124
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发表时间:
2011-07
影响因子:
14.9
通讯作者:
Koito A
Koito A
中科院分区:
生物学2区
文献类型:
--
作者:
Ikeda T;Abd El Galil KH;Tokunaga K;Maeda K;Sata T;Sakaguchi N;Heidmann T;Koito A

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APOBEC3(A3)基因编码的哺乳动物胞苷脱氨酶限制多种内源性逆转录元件和外源性逆转录病毒(包括鼠白血病病毒和人类免疫缺陷病毒(HIV)-1)的能力现已得到充分证实。来自多种哺乳动物的RNA编辑家族成员载脂蛋白B(apo B)编辑催化亚基1(APOBEC1;A1),一种参与脂质转运并介导apo B的mRNA的C - U脱氨的蛋白质,也已被证明可修饰一系列外源性逆转录病毒,但其对内源性逆转录元件的活性仍不清楚。在此,我们在基于细胞培养的逆转录转座分析中表明,来自多种哺乳动物的A1家族蛋白也可降低LINE - 1(长散在核苷酸序列 - 1,L1)和长末端重复序列(LTR)逆转录转座子(或内源性逆转录病毒),如鼠内质网A颗粒(IAP)和MusD序列的移动性和感染潜力。A1的抗L1活性主要由一种不依赖脱氨的机制介导,并且不受蛋白质亚细胞定位的影响。相比之下,对LTR - 逆转录转座子的抑制似乎需要A1蛋白的脱氨酶活性。因此,包括A1在内的AID/APOBEC家族蛋白采用多种机制来调节几种哺乳动物中自主逆转录转座子的移动性。
The ability of mammalian cytidine deaminases encoded by the APOBEC3 (A3) genes to restrict a broad number of endogenous retroelements and exogenous retroviruses, including murine leukemia virus and human immunodeficiency virus (HIV)-1, is now well established. The RNA editing family member apolipoprotein B (apo B)-editing catalytic subunit 1 (APOBEC1; A1) from a variety of mammalian species, a protein involved in lipid transport and which mediates C–U deamination of mRNA for apo B, has also been shown to modify a range of exogenous retroviruses, but its activity against endogenous retroelements remains unclear. Here, we show in cell culture-based retrotransposition assays that A1 family proteins from multiple mammalian species can also reduce the mobility and infectivity potential of LINE-1 (long interspersed nucleotide sequence-1, L1) and long-terminal repeats (LTRs) retrotransposons (or endogenous retroviruses), such as murine intracisternal A-particle (IAP) and MusD sequences. The anti-L1 activity of A1 was mainly mediated by a deamination-independent mechanism, and was not affected by subcellular localization of the proteins. In contrast, the inhibition of LTR-retrotransposons appeared to require the deaminase activity of A1 proteins. Thus, the AID/APOBEC family proteins including A1s employ multiple mechanisms to regulate the mobility of autonomous retrotransposons in several mammalian species.
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