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病毒因子Tat对HIV-1基因表达的RNA识别与调控

RNA recognition and regulation of HIV-1 gene expression by viral factor Tat.

作者信息

Naryshkin N A, Gait M J, Ivanovskaya M G

机构信息

Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119899, Russia.

出版信息

Biochemistry (Mosc). 1998 May;63(5):489-503.

PMID:9632883
Abstract

Viral transcription factor Tat is a small nuclear protein containing a large number of basic amino acids. The tat gene consists of two exons but only the first encoding 72-amino acid polypeptide is necessary for protein activity. Since the second exon is poorly conservative the total number of amino acids among Tat proteins from different strains of HIV-1 varies from 86 to 130. Tat protein acts as trans-activator of HIV genome transcription. It is absolutely required for viral functioning. Tat increases processivity of RNA-polymerase II by abolition of transcription blockade, which appears after polycondensation of the first 60-70 nucleotides of either HIV mRNA, i.e., it acts as antiterminator. For manifestation of its activity Tat specifically binds to the double stranded RNA fragment called TAR which is located at the 5'-terminus of all HIV mRNAs. The TAR structure contains a hairpin and a side loop. The Tat-binding region includes only a site of the loop; manifestation of Tat activity in vivo requires the full TAR and additional cellular co-factors.

摘要

病毒转录因子Tat是一种含有大量碱性氨基酸的小核蛋白。tat基因由两个外显子组成,但只有第一个编码72个氨基酸的多肽对蛋白质活性是必需的。由于第二个外显子保守性较差,来自不同HIV-1毒株的Tat蛋白之间的氨基酸总数在86到130之间变化。Tat蛋白作为HIV基因组转录的反式激活因子。它是病毒功能绝对必需的。Tat通过消除转录阻断来增加RNA聚合酶II的持续合成能力,这种转录阻断在HIV mRNA前60-70个核苷酸缩合后出现,即它起抗终止子的作用。为了表现其活性,Tat特异性结合位于所有HIV mRNA 5'-末端的称为TAR的双链RNA片段。TAR结构包含一个发夹和一个侧环。Tat结合区域仅包括环的一个位点;Tat在体内的活性表现需要完整的TAR和额外的细胞辅助因子。

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