Absence of DICER in Monocytes and Its Regulation by HIV-1
Absence of DICER in Monocytes and Its Regulation by HIV-1
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DOI：
10.1074/jbc.m110.101709
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发表时间：
2010-10-15
影响因子：
4.8
通讯作者：
Kashanchi, Fatah
中科院分区：
文献类型：
--
作者：
Coley, William;Van Duyne, Rachel;Kashanchi, Fatah
MicroRNAs(MiRNAs)是一类小的RNA分子，其功能是控制基因表达和限制病毒在宿主细胞中的复制。MiRNAs的产生被认为依赖于Disher酶。现有证据表明，在T淋巴细胞中，HIV-1既可以抑制宿主的miRNA途径，也可以为了自身的利益而共同选择宿主的miRNA途径。在这项研究中，我们研究了单核细胞和巨噬细胞miRNA的产生状态，以及病毒感染对miRNA产生的影响。一般来说，单核细胞表达少量的miRNA相关蛋白，尤其是迪格尔，直到单核细胞分化为巨噬细胞后才能检测到。在分化前存在HIV-1的情况下，DICER的表达被抑制。从转基因和处理细胞中提取的RNA的MicroRNA芯片结果表明，miRNA产量的下降与巨噬细胞中Dird蛋白的抑制是一致的。我们发现单核细胞中DICER的表达受miR-106a的限制，但HIV-1通过病毒基因vpr抑制了DICER的表达。此外，对单核细胞和巨噬细胞中miRNA表达的分析表明，一些miRNAs可以被Dever和PIWIL4处理。这里提出的结果对巨噬细胞中病毒感染的病理学和miRNAs的生物发生都有意义。首先，HIV-1通过一种先前未知的机制抑制巨噬细胞中DICER的表达和功能。其次，缺乏DICER的单核细胞中存在miRNAs，这表明一些miRNAs可以由DICER以外的蛋白质产生。
MicroRNAs (miRNAs) are a class of small RNA molecules that function to control gene expression and restrict viral replication in host cells. The production of miRNAs is believed to be dependent upon the DICER enzyme. Available evidence suggests that in T lymphocytes, HIV-1 can both suppress and co-opt the host's miRNA pathway for its own benefit. In this study, we examined the state of miRNA production in monocytes and macrophages as well as the consequences of viral infection upon the production of miRNA. Monocytes in general express low amounts of miRNA-related proteins, and DICER in particular could not be detected until after monocytes were differentiated into macrophages. In the case where HIV-1 was present prior to differentiation, the expression of DICER was suppressed. MicroRNA chip results for RNA isolated from transfected and treated cells indicated that a drop in miRNA production coincided with DICER protein suppression in macrophages. We found that the expression of DICER in monocytes is restricted by miR-106a, but HIV-1 suppressed DICER expression via the viral gene Vpr. Additionally, analysis of miRNA expression in monocytes and macrophages revealed evidence that some miRNAs can be processed by both DICER and PIWIL4. Results presented here have implications for both the pathology of viral infections in macrophages and the biogenesis of miRNAs. First, HIV-1 suppresses the expression and function of DICER in macrophages via a previously unknown mechanism. Second, the presence of miRNAs in monocytes lacking DICER indicates that some miRNAs can be generated by proteins other than DICER.