Suppression of microRNA-silencing pathway by HIV-1 during virus replication

Suppression of microRNA-silencing pathway by HIV-1 during virus replication
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DOI:
10.1126/science.1136319
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发表时间:
2007-03-16
期刊:
影响因子:
56.9
通讯作者:
Benkirane, Monsef
Benkirane, Monsef
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Triboulet, Robinson;Mari, Bernard;Benkirane, Monsef

文献摘要

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MicroRNAs (miRNAs)是一种19 - 25个核苷酸的单链非编码RNA,其功能是基因调节因子和宿主细胞防御RNA和DNA病毒。我们为mirna沉默机制在控制HIV-1复制中的生理作用提供了证据。负责miRNA加工的III型rna酶Dicer和Drosha在hiv -1感染供者的外周血单个核细胞和潜伏感染细胞中抑制病毒复制。反过来,HIV-1积极抑制多顺反子miRNA簇miR-17/92的表达。这种抑制被发现是有效的病毒复制所必需的,并且依赖于组蛋白乙酰转移酶Tat辅助因子PCAF。我们的研究结果强调了mirna沉默途径在HIV-1复制和潜伏期中的参与。
MicroRNAs ( miRNAs) are single-stranded noncoding RNAs of 19 to 25 nucleotides that function as gene regulators and as a host cell defense against both RNA and DNA viruses. We provide evidence for a physiological role of the miRNA-silencing machinery in controlling HIV-1 replication. Type III RNAses Dicer and Drosha, responsible for miRNA processing, inhibited virus replication both in peripheral blood mononuclear cells from HIV-1-infected donors and in latently infected cells. In turn, HIV-1 actively suppressed the expression of the polycistronic miRNA cluster miR-17/92. This suppression was found to be required for efficient viral replication and was dependent on the histone acetyltransferase Tat cofactor PCAF. Our results highlight the involvement of the miRNA-silencing pathway in HIV-1 replication and latency.