Feng S, Holland E C
Department of Biochemistry, Stanford University Medical Center, California 94305.
Nature. 1988 Jul 14;334(6178):165-7. doi: 10.1038/334165a0.
Human immunodeficiency virus (HIV-1) is the primary retroviral agent responsible for AIDS and related disorders worldwide. One of its identified gene products, tat protein, stimulates in trans the expression of all HIV-1 genes by several orders of magnitude. Cells infected with HIV-1 require tat protein to produce virus, suggesting that trans-activation is crucial for viral replication. The essential cis-acting site for trans-activation, termed tar, resides within the R region of the HIV-1 long terminal repeat (LTR), between -17 and +54 with respect to the initiation site of viral transcription. It is striking that the RNA encoded between +1 and +59 has the potential to form an extensive stem-loop secondary structure which, as a portion of the untranslated leader RNA, would be common to all HIV-1 mRNAs. We now present the results of nucleotide substitution experiments which suggest that tat trans-activation requires presentation of the sequence +30CUGGG+34 in tar within the loop of a RNA hairpin structure.
人类免疫缺陷病毒1型（HIV-1）是全球范围内导致艾滋病及相关疾病的主要逆转录病毒病原体。其已确定的基因产物之一，即反式激活转录蛋白（tat蛋白），可使所有HIV-1基因的表达在转录水平上提高几个数量级。感染HIV-1的细胞产生病毒需要tat蛋白，这表明反式激活对于病毒复制至关重要。反式激活所必需的顺式作用位点，称为tar，位于HIV-1长末端重复序列（LTR）的R区域内，相对于病毒转录起始位点为-17至+54。引人注目的是，+1至+59之间编码的RNA有可能形成广泛的茎环二级结构，作为未翻译前导RNA的一部分，这将是所有HIV-1 mRNA所共有的。我们现在展示核苷酸取代实验的结果，这些结果表明tat反式激活需要在RNA发夹结构环内的tar中呈现序列+30CUGGG+34。
