All APOBEC3 family proteins differentially inhibit LINE-1 retrotransposition.
All APOBEC3 family proteins differentially inhibit LINE-1 retrotransposition.
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DOI：
10.1093/nar/gkm181
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发表时间：
2007
影响因子：
14.9
通讯作者：
Tokunaga, Kenzo
中科院分区：
文献类型：
--
作者：
Kinomoto, Masanobu;Kanno, Takayuki;Shimura, Mari;Ishizaka, Yukihito;Kojima, Asato;Kurata, Takeshi;Sata, Tetsutaro;Tokunaga, Kenzo
大约17%的人类基因组由长散布的核元件1 （LINE-1, L1）非ltr反转录转座子组成。已知L1反转录转位是几种遗传性疾病的病因，如血友病A、杜氏肌营养不良等。L1逆转录因子也能引起结肠癌，这表明如果先天免疫功能不正常，L1转位不仅可能发生在生殖细胞中，也可能发生在体细胞中。然而，正常细胞中L1转位限制的机制尚未完全确定。我们在这里表明，抗逆转录病毒先天蛋白，人类APOBEC3 （hA3）家族成员，从hA3A到hA3H，不同地降低L1逆转录转位水平，这与对vif缺陷的HIV-1和小鼠白血病病毒的抗病毒活性无关，也与亚细胞定位模式无关。重要的是，hA3G蛋白抑制L1逆转录，这与最近的报道形成鲜明对比。hA3家族成员对L1转位的抑制作用可能不是由于脱氨酶活性，而是由于新的机制。因此，我们得出结论，所有的hA3蛋白都有不同的抑制L1元件不受控制的转位的作用。
Approximately 17% of the human genome is comprised of long interspersed nuclear element 1 (LINE-1, L1) non-LTR retrotransposons. L1 retrotransposition is known to be the cause of several genetic diseases, such as hemophilia A, Duchene muscular dystrophy, and so on. The L1 retroelements are also able to cause colon cancer, suggesting that L1 transposition could occur not only in germ cells, but also in somatic cells if innate immunity would not function appropriately. The mechanisms of L1 transposition restriction in the normal cells, however, are not fully defined. We here show that antiretroviral innate proteins, human APOBEC3 (hA3) family members, from hA3A to hA3H, differentially reduce the level of L1 retrotransposition that does not correlate either with antiviral activity against Vif-deficient HIV-1 and murine leukemia virus, or with patterns of subcellular localization. Importantly, hA3G protein inhibits L1 retrotransposition, in striking contrast to the recent reports. Inhibitory effect of hA3 family members on L1 transposition might not be due to deaminase activity, but due to novel mechanism(s). Thus, we conclude that all hA3 proteins act to differentially suppress uncontrolled transposition of L1 elements.