Derepression of MicroRNA-mediated protein translation inhibition by apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G) and its family members
Derepression of MicroRNA-mediated protein translation inhibition by apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G) and its family members
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DOI：
10.1074/jbc.m705116200
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发表时间：
2007-11-16
影响因子：
4.8
通讯作者：
Zhang, Hui
中科院分区：
文献类型：
--
作者：
Huang, Jialing;Liang, Zhihui;Zhang, Hui
载脂蛋白 B mRNA 编辑酶催化多肽样 3G（APOBEC3G 或 A3G）及其胞苷脱氨酶家族成员是人类免疫缺陷病毒 1 型 (HIV-1) 和许多其他逆转录病毒的有效限制因素。 A3G 与多种 RNA 结合蛋白相互作用，位于加工体和应激颗粒中。然而，其细胞功能仍有待进一步阐明。使用荧光素酶报告基因和绿色荧光蛋白报告基因，我们证明 A3G 和其他 APOBEC 家族成员可以抵消各种 microRNA (miRNA)（例如 mir-10b、mir-16、mir-25 和 let-7a）对蛋白质合成的抑制。 A3G 还可以增强 miRNA 靶向 mRNA 的表达水平。此外，A3G 促进了 microRNA 靶向 mRNA 与多聚核糖体的关联，而不是与加工体的关联。有趣的是，C288A/C291A A3G 突变体的实验表明，A3G 的这种功能与其胞苷脱氨酶活性是分开的。我们的研究结果表明，A3G 的主要细胞功能除了抑制逆转录转座子的移动性和内源性逆转录病毒的复制之外，最有可能防止加工体中 miRNA 靶向 mRNA 的衰变。
The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G or A3G) and its fellow cytidine deaminase family members are potent restrictive factors for human immunodeficiency virus type 1 (HIV-1) and many other retroviruses. A3G interacts with a vast spectrum of RNA-binding proteins and is located in processing bodies and stress granules. However, its cellular function remains to be further clarified. Using a luciferase reporter gene and green fluorescent protein reporter gene, we demonstrate that A3G and other APOBEC family members can counteract the inhibition of protein synthesis by various microRNAs ( miRNAs) such as mir-10b, mir-16, mir-25, and let-7a. A3G could also enhance the expression level of miRNA-targeted mRNA. Further, A3G facilitated the association of microRNA-targeted mRNA with polysomes rather than with processing bodies. Intriguingly, experiments with a C288A/C291A A3G mutant indicated that this function of A3G is separable from its cytidine deaminase activity. Our findings suggest that the major cellular function of A3G, in addition to inhibiting the mobility of retrotransposons and replication of endogenous retroviruses, is most likely to prevent the decay of miRNA-targeted mRNA in processing bodies.