ADAR1 restricts LINE-1 retrotransposition.
ADAR1 restricts LINE-1 retrotransposition.
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DOI：
10.1093/nar/gkw834
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发表时间：
2017-01-09
影响因子：
14.9
通讯作者：
Michienzi A
中科院分区：
文献类型：
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作者：
Orecchini E;Doria M;Antonioni A;Galardi S;Ciafrè SA;Frassinelli L;Mancone C;Montaldo C;Tripodi M;Michienzi A
作用于RNA的腺苷脱氨酶（ADAR）参与将双链RNA中的腺苷转化为肌苷的RNA编辑。ADAR 1被证明对不同的病毒发挥抗病毒或前病毒作用。关于HIV-1，一些研究表明ADAR 1有利于病毒复制。本研究的目的是调查组成的ADAR 1核糖核蛋白复合物在HIV-1的表达。通过在表达HIV-1的细胞中使用双标签亲和纯化程序，然后进行质谱分析，我们确定了14个非核糖体ADAR 1相互作用蛋白，其中大多数是新的。这些蛋白质的显著部分先前被证明与长间隔元件1（LINE 1或L1）核糖核颗粒相关，并调节连续重新进入宿主基因组的L1反转录转座子的生命周期。因此，我们研究了ADAR 1在调节L1活性中的功能。通过在HeLa细胞中使用不同的基于细胞培养的反转录转座试验，我们证明了ADAR 1作为L1反转录转座抑制剂的新功能。显然，这种抑制机制不是通过ADAR 1编辑活性发生的。此外，我们发现ADAR 1结合基底L1 RNP复合物。总体而言，这些数据支持ADAR 1作为L1生命周期调节因子的作用。
Adenosine deaminases acting on RNA (ADARs) are involved in RNA editing that converts adenosines to inosines in double-stranded RNAs. ADAR1 was demonstrated to be functional on different viruses exerting either antiviral or proviral effects. Concerning HIV-1, several studies showed that ADAR1 favors viral replication. The aim of this study was to investigate the composition of the ADAR1 ribonucleoprotein complex during HIV-1 expression. By using a dual-tag affinity purification procedure in cells expressing HIV-1 followed by mass spectrometry analysis, we identified 14 non-ribosomal ADAR1-interacting proteins, most of which are novel. A significant fraction of these proteins were previously demonstrated to be associated to the Long INterspersed Element 1 (LINE1 or L1) ribonucleoparticles and to regulate the life cycle of L1 retrotransposons that continuously re-enter host-genome. Hence, we investigated the function of ADAR1 in the regulation of L1 activity. By using different cell-culture based retrotransposition assays in HeLa cells, we demonstrated a novel function of ADAR1 as suppressor of L1 retrotransposition. Apparently, this inhibitory mechanism does not occur through ADAR1 editing activity. Furthermore, we showed that ADAR1 binds the basal L1 RNP complex. Overall, these data support the role of ADAR1 as regulator of L1 life cycle.