TAT TRANS-ACTIVATES THE HUMAN IMMUNODEFICIENCY VIRUS THROUGH A NASCENT RNA TARGET

TAT TRANS-ACTIVATES THE HUMAN IMMUNODEFICIENCY VIRUS THROUGH A NASCENT RNA TARGET
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DOI:
10.1016/0092-8674(89)90289-4
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发表时间:
1989-10-20
期刊:
影响因子:
64.5
通讯作者:
JEANG, KT
JEANG, KT
中科院分区:
生物学1区
文献类型:
--
作者:
BERKHOUT, B;SILVERMAN, RH;JEANG, KT

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人类免疫缺陷病毒 1 型 (HIV-1) 基因组的表达很大程度上依赖于病毒反式激活蛋白 Tat。 Tat 通过 TAR 元件发挥作用,该元件在病毒 DNA 和 RNA 中都有体现。目前,还没有明确的证据表明 Tat 是通过 DNA 还是 RNA 形式的 TAR 发挥作用。我们使用分子内诱变方法选择性地改变 TAR 的 RNA 二级结构,而不影响其一级序列。我们证明 TAR 的特定 RNA 二级结构是生物活性所必需的。此外,仅短暂形成天然 TAR RNA 发夹(成熟 mRNA 中不保留)的转录物完全被 Tat 反式激活,表明 TAR 被识别为新生 RNA。
Expression of the human immunodeficiency virus type 1 (HIV-1) genome is greatly dependent on the viral trans-activator protein Tat. Tat functions through the TAR element, which is represented in both viral DNA and RNA. At present, there is no definitive evidence that determines whether Tat acts through a DNA or RNA form of TAR. We have used an intramolecular mutagenesis approach to change selectively the RNA secondary structure of TAR without affecting its primary sequence. We show that a specific RNA secondary structure for TAR is needed for biological activity. Furthermore, transcripts that only transiently form a native TAR RNA hairpin, which is not maintained in the mature mRNA, are completely trans-activated by Tat, suggesting that TAR is recognized as a nascent RNA.