Inhibition of SNAP25 expression by HIV-1 Tat involves the activity of mir-128a
Inhibition of SNAP25 expression by HIV-1 Tat involves the activity of mir-128a
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DOI：
10.1002/jcp.21452
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发表时间：
2008-09-01
影响因子：
5.6
通讯作者：
Peruzzi, Francesca
中科院分区：
文献类型：
--
作者：
Eletto, Davide;Russo, Giuseppe;Peruzzi, Francesca
Micro RNA（牛奶）是短的内源性 RNA，通过与信使 RNA 不完全配对来调节基因表达。越来越多的研究表明，哺乳动物微小RNA在细胞功能的各个方面发挥着重要作用，包括分化、增殖和细胞死亡。最近的研究结果表明，成熟神经元树突中存在 microRNA，表明它们可能参与控制合法蛋白质翻译和突触功能。 HIV-1 脑病 (HIVE) 是 HIV-1 感染的一种表现，通常会导致国家损害和功能障碍。虽然神经元很少（如果有的话）被HIV-1感染，但它们暴露于细胞毒性病毒和细胞因子，包括HIV-1反式激活因子Tat。在这项研究中，我们发现 Tat 会解除初级皮质神经元中选定 microRNA（包括神经元 mir-128）的表达水平。我们进一步表明，mir-128a 抑制突触前蛋白 SNAP25 的表达，而抗 mir-128a 部分恢复 Tat/mir-128a 诱导的 SNAP25 表达下调。总而言之，我们的数据提供了一种 HIV-Tat 扰乱神经元活动的新机制。
Micro RNAs (milks) are short endogenous RNAs that regulate gene expression by incomplete pairing with messenger RNAs. An increasing number of studies show that mammalian micro RNAs play fundamental roles in various aspects of cellular function including differentiation, proliferation, and cell death. Recent findings demonstrating the presence of microRNAs in mature neuronal dendrites suggest their possible involvement in controlling legal protein translation and synaptic function. HIV-1 Encephalopathy (HIVE) is a manifestation of HIV-1 infection that often results national damage and dysfunction. While neurons are rarely, if ever, infected by HIV- 1, they are exposed to cytotoxic viral and cellular factors including the HIV-1 transactivating factor Tat. In this study, we show that Tat deregulates expression levels of selected microRNAs, including the neuronal mir-128, in primary cortical neurons. We further show that mir-128a inhibits expression of the pre-synaptic protein SNAP25, whereas the anti-mir-128a partially restores Tat/mir-128a-induced downregulation of SNAP25 expression. Altogether, our data provide a novel mechanism by which HIV-Tat perturbs neuronal activity.