N-myristoyltransferase 1 enhances human immunodeficiency virus replication through regulation of viral RNA expression level.
N-myristoyltransferase 1 enhances human immunodeficiency virus replication through regulation of viral RNA expression level.
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N-肉豆蔻酰转移酶 1 通过调节病毒 RNA 表达水平来增强人类免疫缺陷病毒的复制。
DOI：
10.1016/j.bbrc.2015.06.047
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Misumi S.
中科院分区：
文献类型：
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作者：
Ohta H;Takamune N;Kishimoto N;Shoji S;Misumi S.
N-肉豆蔻酰转移酶 (NMT) 催化蛋白质 N-肉豆蔻酰化。研究表明同工酶 NMT1 可以增强 1 型人类免疫缺陷病毒 (HIV-1) 的复制。然而，NMT1 的机制细节仍不清楚。在这项研究中，我们通过免疫共沉淀和质谱研究了 NMT1 结合蛋白。结果，观察到包括核糖体蛋白、NMT 同工酶和 hnRNP A2/B1 在内的几种 RNA 结合蛋白主要通过 RNA 介导与 NMT1 结合。有趣的是，仅 hRNP A2/B1 被发现与 NMT1 相关，无需 RNA 介导。还表明 hnRNP A2/B1 有助于形成涉及 NMT1 的高分子量复合物。 hnRNP A2/B1 的敲低导致病毒复制增强，产生 HIV-1 的细胞中病毒 RNA 的表达水平增加。另一方面，NMT1的敲低导致病毒复制减弱，产生HIV-1的细胞中病毒RNA的表达水平降低。此外，NMT1的过度表达导致病毒复制增强，病毒RNA表达水平增加。这些发现表明，NMT1 和 hnRNP A2/B1 通过对产生 HIV-1 的细胞中的病毒 RNA 表达产生相反的作用，从而参与 HIV-1 RNA 表达的调节。
N-myristoyltransferase (NMT) catalyzes proteinN-myristoylation. It has been suggested that the isozyme NMT1 enhances the replication of human immunodeficiency virus type-1 (HIV-1). However, the details of the mechanism by which NMT1 does so remain unclear. In this study, we investigated NMT1-binding proteins by co-immunoprecipitation and mass spectrometry. As a result, several RNA-binding proteins including ribosomal proteins, NMT isozymes, and hnRNP A2/B1 were observed to bind to NMT1, as mediated mainly by RNA. Interestingly, only hRNP A2/B1 was found to associate with NMT1 without mediation by RNA. It was also suggested that hnRNP A2/B1 contributes to the formation of complexes of high molecular weights involving NMT1. Knockdown of hnRNP A2/B1 resulted in the enhancement of viral replication with an increase in the expression level of viral RNA in HIV-1-producing cells. On the other hand, knockdown of NMT1 resulted in the attenuation of viral replication with the decrease in the expression level of viral RNA in HIV-1-producing cells. Additionally, overexpression of NMT1 induced the enhancement of viral replication with the increase in the expression level of the viral RNA. These findings suggest that both NMT1 and hnRNP A2/B1 take part in the regulation of HIV-1 RNA expression through their mutual opposite effects on the viral RNA expression in HIV-1-producing cells.