Human cellular microRNA hsa-miR-29a interferes with viral nef protein expression and HIV-1 replication.
Human cellular microRNA hsa-miR-29a interferes with viral nef protein expression and HIV-1 replication.
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DOI：
10.1186/1742-4690-5-117
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发表时间：
2008-12-23
期刊：
影响因子：
3.3
通讯作者：
Brahmachari SK
中科院分区：
文献类型：
--
作者：
Ahluwalia JK;Khan SZ;Soni K;Rawat P;Gupta A;Hariharan M;Scaria V;Lalwani M;Pillai B;Mitra D;Brahmachari SK
细胞mirna在真核生物基因表达调控中发挥着重要作用。最近，mirna也被证明能够靶向和抑制病毒基因的表达。先前的计算预测显示，HIV-1基因组包含可能被人类mirna潜在靶向的区域。在这里，我们报告了预测的miR-29a靶位点在HIV-1 nef基因中的功能。我们发现人mirna hsa-miR-29a和29b在人外周血单核细胞中表达。与不含靶位点的荧光素酶构建体相比，携带nef miR-29a靶位点的荧光素酶报告基因的表达减少。锁定的核酸修饰的靶向hsa-miR-29a和29b的抗miRNAs特异性地逆转了细胞miRNAs在靶位点介导的抑制作用。miRNA的异位表达导致靶Nef蛋白的抑制和病毒水平的降低。我们的研究结果表明，细胞miRNA hsa-miR29a下调Nef蛋白的表达并干扰HIV-1的复制。
Cellular miRNAs play an important role in the regulation of gene expression in eukaryotes. Recently, miRNAs have also been shown to be able to target and inhibit viral gene expression. Computational predictions revealed earlier that the HIV-1 genome includes regions that may be potentially targeted by human miRNAs. Here we report the functionality of predicted miR-29a target site in the HIV-1 nef gene. We find that the human miRNAs hsa-miR-29a and 29b are expressed in human peripheral blood mononuclear cells. Expression of a luciferase reporter bearing the nef miR-29a target site was decreased compared to the luciferase construct without the target site. Locked nucleic acid modified anti-miRNAs targeted against hsa-miR-29a and 29b specifically reversed the inhibitory effect mediated by cellular miRNAs on the target site. Ectopic expression of the miRNA results in repression of the target Nef protein and reduction of virus levels. Our results show that the cellular miRNA hsa-miR29a downregulates the expression of Nef protein and interferes with HIV-1 replication.
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影响因子：
14.9
作者：
Rusinov, V;Baev, V;Minkov, IN;Tabler, M
通讯作者：
Tabler, M
影响因子：
3.3
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Omoto S;Ito M;Tsutsumi Y;Ichikawa Y;Okuyama H;Brisibe EA;Saksena NK;Fujii YR
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Fujii YR
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Sarnow, P
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影响因子：
3.1
作者：
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Wan, Da-Zhi