STRUCTURE-FUNCTION ANALYSES OF THE HTLV-I REX AND HIV-1 REV RNA RESPONSE ELEMENTS - INSIGHTS INTO THE MECHANISM OF REX AND REV ACTION
STRUCTURE-FUNCTION ANALYSES OF THE HTLV-I REX AND HIV-1 REV RNA RESPONSE ELEMENTS - INSIGHTS INTO THE MECHANISM OF REX AND REV ACTION
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DOI：
10.1101/gad.4.6.1014
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发表时间：
1990-06-01
影响因子：
10.5
通讯作者：
GREENE, WC
中科院分区：
文献类型：
--
作者：
AHMED, YF;HANLY, SM;GREENE, WC
I型人t细胞白血病病毒（HTLV-I）的Rex蛋白在转录后调控逆转录病毒gag和环境结构基因表达的能力严重依赖于Rex应答元件（RexRE）的存在。这个顺式调控序列位于逆转录病毒3”长末端重复序列中，与预测的高度稳定的RNA茎环结构一致。雷克斯的活动既需要雷克斯固有的整个二级结构，也需要来自这个大结构的一个小区域的特定序列。这个小的亚区可能形成Rex的蛋白质结合位点或细胞rna结合因子。虽然Rex可以通过与类似的Rev反应元件（RevRE）的相互作用在功能上取代I型人类免疫缺陷病毒（HIV-1）的Rev蛋白，但该HIV-1 RNA元件的不同亚区介导对Rex和Rev的反应。引人注目的是，在RevRE的Rex反应亚区缺失后，Rex作为Rev作用的主要抑制因子。同样，当Rev的Rev响应子区域被删除时，Rev以显性方式抑制Rex功能。总之，这些发现表明，Rex和Rev不仅与各自的RNA反应元件相互作用，而且可能形成混合的非活性多聚体或与共同的细胞因子相互作用。如果涉及到共同宿主蛋白的结合，该因子可能在剪接体组装或核RNA运输中起核心作用。
The ability of the Rex protein of the type I human T-cell leukemia virus (HTLV-I) to regulate expression of the retroviral gag and env structural genes post-transcriptionally is critically dependent on the presence of a Rex response element (RexRE). This cis-regulatory sequence is located within the retroviral 3'' long terminal repeat and coincides with a predicted, highly stable RNA stem-loop structure. Rex action requires both the overall secondary structure intrinsic to the RexRe and specific sequences from one small subregion of this large structure. This small subregion likley forms a protein-binding site for Rex or a cellular RNA-binding factor. Whereas Rex can functionally replace the Rev protein of the type I human immunodeficiency virus (HIV-1) through its interaction with the analogous Rev response element (RevRE), distinct subregions of this HIV-1 RNA element mediate the responses to Rex and REv. Strikingly, Rex acts as a dominant repressor of Rev action, following the deletion of the Rex responsive subregion of the RevRe. Similarly, Rev inhibits Rex function in a dominant manner when the Rev responsive subregion of the RevRe is deleted. Together, these findings suggest that Rex and Rev not only interact with their respective RNA response elements but also may either form mixed inactive multimers or interact with a common cellular factor(s). If binding of a common host protein is involved, this factor likely plays a central role either in spliceosome assembly or nuclear RNA transport.