ACTIVATION OF HIV-1 PREMESSENGER RNA 3' PROCESSING INVITRO REQUIRES BOTH AN UPSTREAM ELEMENT AND TAR
ACTIVATION OF HIV-1 PREMESSENGER RNA 3' PROCESSING INVITRO REQUIRES BOTH AN UPSTREAM ELEMENT AND TAR
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DOI：
10.1002/j.1460-2075.1992.tb05542.x
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发表时间：
1992-12-01
期刊：
影响因子：
11.4
通讯作者：
OETJEN, J
中科院分区：
文献类型：
--
作者：
GILMARTIN, GM;FLEMING, ES;OETJEN, J
人类免疫缺陷病毒1型(HIV-1)基因组的结构给病毒转录本的3‘端处理带来了一个有趣的两难境地--忽略了转录本5’端存在的规范的‘核心’聚(A)位点处理信号，而又有效地利用了位于消息3‘端的相同信号。HIV-1中加工位点的选择似乎受到两个因素的影响：(I)是否接近帽部位，以及(Ii)核心聚(A)位点上游的序列。我们现在证明，位于U3区域内的一个体内定义的上游元件，位于AAUAAA六角体上游的76个核苷酸，在体外特异性地增强HIV-1核心聚(A)位点的3‘加工。我们进一步证明，有效的体外3‘加工需要TAR的RNA茎环结构，这是为了在空间上并列上游元件和核心聚(A)位点。对HIV-1聚(A)位点形成的3‘加工复合体的稳定性分析表明，上游元件可能通过增加核心聚(A)位点的加工复合体的稳定性而发挥作用。
The architecture of the human immunodeficiency virus type 1 (HIV-1) genome presents an intriguing dilemma for the 3' processing of viral transcripts-to disregard a canonical 'core' poly(A) site processing signal present at the 5' end of the transcript and yet to utilize efficiently an identical signal that resides at the 3' end of the message. The choice of processing sites in HIV-1 appears to be influenced by two factors: (i) proximity to the cap site, and (ii) sequences upstream of the core poly(A) site. We now demonstrate that an in vivo-defined upstream element that resides within the U3 region, 76 nucleotides upstream of the AAUAAA hexamer, acts specifically to enhance 3' processing at the HIV-1 core poly(A) site in vitro. We furthermore show that efficient in vitro 3' processing requires the RNA stem-loop structure of TAR, which serves to juxtapose spatially the upstream element and the core poly(A) site. An analysis of the stability of 3' processing complexes formed at the HIV-1 poly(A) site in vitro suggests that the upstream element may function by increasing processing complex stability at the core poly(A) site.