Negative regulation of gene expression from the HTLV type II long terminal repeat by Rex: functional and structural dissociation from positive posttranscriptional regulation.
Negative regulation of gene expression from the HTLV type II long terminal repeat by Rex: functional and structural dissociation from positive posttranscriptional regulation.
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Rex 对 HTLV II 型长末端重复基因表达的负调控：与正转录后调控的功能和结构分离。
DOI：
10.1089/aid.1996.12.535
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Black,AC
中科院分区：
文献类型：
--
作者：
Watanabe,CT;Rosenblatt,JD;Bakker,A;Morgan,JP;Luo,J;Chun,S;Black,AC
雷克斯对人类T细胞白血病病毒II型（HTLV-II）基因表达的调节是由5 '病毒长末端重复序列（LTR）中的顺式作用元件介导的。雷克斯在转录后发挥作用，增强编码结构蛋白的不完全剪接病毒mRNA的细胞质积累。我们报告了一个独特的负调控功能介导的雷克斯影响表达的病毒5′ LTR。使用LTR驱动的CAT报告和全长HTLV-II前病毒构建体，我们证明了雷克斯以剂量依赖性方式降低含LTR mRNA的总细胞水平。负调控是一个独立的功能，证明了结构和功能的分离，从雷克斯积极的转录后调控。这种负调节作用依赖于核定位序列，但不需要之前定义的Rex反应元件（RxRE）。在T细胞系中观察到负调控，但在B细胞系中未观察到负调控，这表明参与转录后调控的细胞类型特异性因子不同。去除aa 38-80的雷克斯的内部缺失突变体保留了抑制的能力，但没有转录后增加表达，而负调控需要一个以前未表征的羧基末端区域（aa 154-170）。这些发现表明，雷克斯可能同时提供两个功能：降低转录的病毒mRNA的总体水平，并促进核到细胞质的mRNA编码的结构蛋白的出口。雷克斯的负调控功能可能在病毒潜伏期中起作用。
Regulation of human T cell leukemia virus type II (HTLV-II) gene expression by Rex is mediated by cis-acting elements in the 5′ viral long terminal repeat (LTR). Rex acts posttranscriptionally to enhance cytoplasmic accumulation of incompletely spliced viral mRNAs encoding structural proteins. We report a distinct negative regulatory function mediated by Rex affecting expression from the viral 5′ LTR. Using both LTR-driven CAT reporters and a full-length HTLV-II proviral construct, we demonstrate that Rex decreases total cellular levels of LTR-containing mRNA in a dose-dependent manner. Negative regulation is an independent function as demonstrated by structural and functional dissociation from Rex positive posttranscriptional regulation. This negative regulatory action was dependent on nuclear localization sequences, but did not require the previously defined Rex-responsive element (RxRE). Negative regulation was observed in T cell lines but not in B cell lines, suggesting the involvement of cell type-specific factors distinct from those involved in posttranscriptional regulation. An internal deletion mutant of Rex removing aa 38–80 retained the ability to repress, but did not posttranscriptionally increase expression, while negative regulation requires a previously uncharacterized carboxy-terminal region (aa 154–170). These findings suggest that Rex may serve two simultaneous functions: to decrease overall levels of transcribed viral mRNA, and to facilitate nuclear to cytoplasmic export of mRNAs encoding structural proteins. The negative regulatory function of Rex may play a role in viral latency.