APOBEC3G Inhibits MicroRNA-mediated Repression of Translation by Interfering with the Interaction between Argonaute-2 and MOV10
APOBEC3G Inhibits MicroRNA-mediated Repression of Translation by Interfering with the Interaction between Argonaute-2 and MOV10
复制标题
APOBEC3G 通过干扰 Argonaute-2 和 MOV10 之间的相互作用来抑制 MicroRNA 介导的翻译抑制
DOI：
10.1074/jbc.m112.354001
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发表时间：
2012-08-24
影响因子：
4.8
通讯作者：
Zhang, Hui
中科院分区：
文献类型：
--
作者：
Liu, Chao;Zhang, Xue;Zhang, Hui
载脂蛋白B-mRNA编辑酶催化多肽样3G(APOBEC3G或A3G)是人类免疫缺陷病毒1型(HIV-1)等多种逆转录病毒的重要限制性因子。它属于胞苷脱氨酶家族。最近的研究表明，A3G显著抑制了microRNA(MiRNA)介导的翻译抑制。然而，必须澄清这一行动背后的机制。在这份报告中，我们证明了A3G通过抑制Moloney白血病病毒10(MOV10)蛋白与ArgAerte-2(AGO2)之间的相互作用，导致miRNA诱导沉默复合体(MiRISC)的异常组装或异常成熟来抵消miRNA介导的翻译抑制。通过一系列MOV10的缺失，我们发现A3G与MOV10的C末端的一个结构域结合，在那里它竞争性地抑制AGO2与该结构域的结合。A3G和MOV10之间的相互作用依赖于它与一种名为7SL RNA的小RNA的结合。A3G突变体W127L不能与7SL RNA结合，显示出显著不能抵消miRNA介导的翻译抑制的能力。我们的数据显示了一种参与调节miRISC活性的新机制。虽然A3G和MOV10都属于干扰素抗病毒系统，可以抑制HIV-1和其他逆转录病毒，但它们对细胞miRNA活性的相反作用表明，它们在各种细胞功能中发挥着更为复杂的调节作用。
The apolipoprotein-B-mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G or A3G) is a potent restrictive factor for human immunodeficiency virus type 1 (HIV-1) and many other retroviruses. It belongs to the cytidine deaminase family. Recent studies have shown that A3G significantly inhibits microRNA (miRNA)-mediated repression of translation. However, the mechanism underlying this action must be clarified. In this report, we have demonstrated that A3G counteracts miRNA-mediated repression of translation by inhibiting the interaction between moloney leukemia virus 10 (MOV10) protein and Argonaute-2 (AGO2), causing either abnormal assembly or abnormal maturation of miRNA-inducing silencing complex (miRISC). Through a series of MOV10 deletions, we found that A3G binds to a domain at the C terminus in MOV10, where it competitively inhibits the binding of AGO2 to that same domain. The interaction between A3G and MOV10 relies on its association with a small RNA named 7SL RNA. The A3G mutant W127L, which is unable to bind to 7SL RNA, shows significantly incapability to counteract the miRNA-mediated repression of translation. Our data demonstrate a novel mechanism involved in the regulation of miRISC activity. Although both A3G and MOV10 belong to the interferon antiviral system and inhibit HIV-1 and other retroviruses, their opposing effects on the cellular miRNA activity suggest that they play much more complicated regulatory roles in various cellular functions.