The Rev protein of human immunodeficiency virus type 1 counteracts the effect of an AU-rich negative element in the human papillomavirus type 1 late 3' untranslated region-猫眼课题宝

人类免疫缺陷病毒 1 型的 Rev 蛋白抵消了人类乳头瘤病毒 1 型晚期 3 非翻译区中富含 AU 的阴性元件的影响

DOI：

发表时间：

1995

期刊：

Journal of Virology

影响因子：

5.4

通讯作者：

中科院分区：

医学2区

文献类型：

作者：

W. Tan;S. Schwartz

我们已经在人乳头瘤病毒1型mRNAs的3'非翻译区晚期鉴定了一个序列，该序列在转录后抑制基因表达。缺失分析将抑制元件定位于人乳头瘤病毒1型基因组上核苷酸6958和6984之间的富含AU的序列。该序列以方向依赖性方式抑制基因表达。用含有该序列的质粒转染真核细胞后，与缺乏抑制序列的质粒相比，产生约4倍低的细胞质mRNA水平和64至128倍低的蛋白质水平。有趣的是，以有义方向提供猿猴逆转录病毒1型的组成型转运元件抵消了人乳头瘤病毒1型序列产生的抑制作用。抑制作用也可以克服存在的人免疫缺陷病毒1型Rev蛋白的反式和其靶序列，Rev反应元件，顺式。Rev是一种核蛋白，通过促进编码结构蛋白的人类免疫缺陷病毒1型mRNA的核输出发挥作用。我们的研究结果与人乳头瘤病毒1型晚期基因表达模型一致，其中含有人乳头瘤病毒1型抑制序列的mRNA在细胞核中进入非生产性途径，导致mRNA利用效率低下。Rev通过与Rev反应元件相互作用，将含有抑制序列的mRNA引导至生产途径。

We have identified a sequence in the late 3' untranslated region of human papillomavirus type 1 mRNAs that acts posttranscriptionally to repress gene expression. Deletion analysis localized the inhibitory element to an AU-rich sequence between nucleotides 6958 and 6984 on the human papillomavirus type 1 genome. This sequence inhibits gene expression in an orientation-dependent manner. Upon transfection of eucaryotic cells with plasmids containing this sequence, approximately 4-fold-lower cytoplasmic mRNA levels and 64- to 128-fold-lower protein levels were produced compared with those produced by plasmids lacking the inhibitory sequence. Interestingly, providing the constitutive transport element of simian retrovirus type 1 in sense orientation counteracted inhibition exerted by the human papillomavirus type 1 sequence. Inhibition could also be overcome by the presence of human immunodeficiency virus type 1 Rev protein in trans and its target sequence, the Rev-responsive element, in cis. Rev is a nuclear protein and acts by promoting nuclear export of human immunodeficiency virus type 1 mRNAs encoding structural proteins. Our results are consistent with a model for human papillomavirus type 1 late-gene expression in which mRNAs containing human papillomavirus type 1 inhibitory sequences enter a nonproductive route in the nucleus, resulting in inefficient mRNA utilization. Rev directs mRNA containing inhibitory sequences to a productive route by interacting with the Rev-responsive element.