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反式激活转录激活因子(Tat)通过新生RNA靶点反式激活人类免疫缺陷病毒。

Tat trans-activates the human immunodeficiency virus through a nascent RNA target.

作者信息

Berkhout B, Silverman R H, Jeang K T

机构信息

Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.

出版信息

Cell. 1989 Oct 20;59(2):273-82. doi: 10.1016/0092-8674(89)90289-4.

DOI:10.1016/0092-8674(89)90289-4
PMID:2478293
Abstract

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.

摘要

人类免疫缺陷病毒1型(HIV-1)基因组的表达在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,TAR元件存在于病毒DNA和RNA中。目前,尚无确凿证据确定Tat是通过DNA形式还是RNA形式的TAR起作用。我们采用分子内诱变方法,选择性地改变TAR的RNA二级结构而不影响其一级序列。我们发现TAR具有生物活性需要特定的RNA二级结构。此外,仅短暂形成天然TAR RNA发夹结构(在成熟mRNA中不保留)的转录本可被Tat完全反式激活,这表明TAR被识别为新生RNA。

相似文献

1
Tat trans-activates the human immunodeficiency virus through a nascent RNA target.反式激活转录激活因子(Tat)通过新生RNA靶点反式激活人类免疫缺陷病毒。
Cell. 1989 Oct 20;59(2):273-82. doi: 10.1016/0092-8674(89)90289-4.
2
RNA transcripts of the human immunodeficiency virus transactivation response element can inhibit action of the viral transactivator.
Proc Natl Acad Sci U S A. 1990 Aug;87(15):5817-21. doi: 10.1073/pnas.87.15.5817.
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Efficient trans-activation by the HIV-2 Tat protein requires a duplicated TAR RNA structure.
Nucleic Acids Res. 1990 Apr 11;18(7):1839-46. doi: 10.1093/nar/18.7.1839.
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Human immunodeficiency virus type 1 TAR element revertant viruses define RNA structures required for efficient viral gene expression and replication.1型人类免疫缺陷病毒TAR元件回复病毒确定了有效病毒基因表达和复制所需的RNA结构。
J Virol. 1995 Aug;69(8):4906-13. doi: 10.1128/JVI.69.8.4906-4913.1995.
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HIV-1 Tat protein trans-activates transcription in vitro.
Cell. 1990 Nov 16;63(4):791-802. doi: 10.1016/0092-8674(90)90145-5.
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tat regulates binding of the human immunodeficiency virus trans-activating region RNA loop-binding protein TRP-185.反式激活转录物(tat)调节人类免疫缺陷病毒反式激活区RNA环结合蛋白TRP-185的结合。
Genes Dev. 1991 Nov;5(11):2128-40. doi: 10.1101/gad.5.11.2128.
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Tat-regulated production of multimerized TAR RNA inhibits HIV-1 gene expression.Tat调控的多聚化TAR RNA的产生抑制HIV-1基因表达。
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A bulge structure in HIV-1 TAR RNA is required for Tat binding and Tat-mediated trans-activation.HIV-1 TAR RNA中的一个凸起结构是Tat结合和Tat介导的反式激活所必需的。
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Formation of a small ribonucleoprotein particle between Tat protein and trans-acting response element in human immunodeficiency virus-infected cells.在人类免疫缺陷病毒感染的细胞中,Tat蛋白与反式作用应答元件之间形成小核糖核蛋白颗粒。
J Biol Chem. 1991 Aug 5;266(22):14620-6.
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HIV-1 Tat protein increases transcriptional initiation and stabilizes elongation.
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