Deamination-independent restriction of LINE-1 retrotransposition by APOBEC3H.

Deamination-independent restriction of LINE-1 retrotransposition by APOBEC3H.
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DOI:
10.1038/s41598-017-11344-4
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发表时间:
2017-09-07
期刊:
影响因子:
4.6
通讯作者:
Chelico L
Chelico L
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Feng Y;Goubran MH;Follack TB;Chelico L

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APOBEC3家族的胞嘧啶脱氨酶能够限制逆转录元件的复制,如LINE-1。然而,七种APOBEC3酶在阻止LINE-1逆转录转座中的作用存在差异,APOBEC3介导的LINE-1抑制机制尚不清楚。多年来的主流观点认为,APOBEC3介导的LINE-1抑制是非脱氨基的,依赖于APOBEC3阻断LINE-1逆转录酶DNA聚合或LINE-1RNA进入细胞核的运输。然而,最近的研究表明,APOBEC3A可以在短暂暴露的单链LINE-1cDNA上脱氨基,形成尿嘧啶,从而导致LINE-1cDNA的降解。在本研究中,我们证实APOBEC3A是一种有效的脱胺依赖的LINE-1反转录转座抑制物,但相反,A3H型单倍型II和单倍型V通过脱胺非依赖性机制限制LINE-1的活性。我们的研究支持不同的APOBEC3蛋白通过不同的机制进化来抑制LINE-1逆转录转座的模型。
The APOBEC3 family of cytosine deaminase enzymes are able to restrict replication of retroelements, such as LINE-1. However, each of the seven APOBEC3 enzymes have been reported to act differentially to prevent LINE-1 retrotransposition and the mechanisms of APOBEC3-mediated LINE-1 inhibition has not been well understood. The prevailing view for many years was that APOBEC3-mediated LINE-1 inhibition was deamination-independent and relied on APOBEC3s blocking the LINE-1 reverse transcriptase DNA polymerization or transport of the LINE-1 RNA into the nucleus. However, recently it was shown that APOBEC3A can deaminate cytosine, to form uracil, on transiently exposed single-stranded LINE-1 cDNA and this leads to LINE-1 cDNA degradation. In this study, we confirmed that APOBEC3A is a potent deamination-dependent inhibitor of LINE-1 retrotransposition, but show that in contrast, A3H haplotype II and haplotype V restrict LINE-1 activity using a deamination-independent mechanism. Our study supports the model that different APOBEC3 proteins have evolved to inhibit LINE-1 retrotransposition through distinct mechanisms.
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