Rev-mediated nuclear export of RNA is dominant over nuclear retention and is coupled to the Ran-GTPase cycle
Rev-mediated nuclear export of RNA is dominant over nuclear retention and is coupled to the Ran-GTPase cycle
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DOI：
10.1093/nar/27.21.4128
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发表时间：
1999-11-01
影响因子：
14.9
通讯作者：
Malim, MH
中科院分区：
文献类型：
--
作者：
Fischer, U;Pollard, VW;Malim, MH
人类免疫缺陷病毒 1 型 Rev 蛋白诱导含有内含子的病毒 mRNA 的核输出，该 mRNA 包含其结合位点，Rev 响应元件 (RRE)，Rev 的富含亮氨酸区域（激活结构域）对于功能至关重要，并已被证明是核输出信号 (NES)。在这里，我们证明 Rev 能够诱导含有可剪接和不可剪接 RRE 的前 mRNA 的输出，并且这种活性不依赖于 RRE 在 RNA 中的位置。重要的是，即使是通过非前mRNA机制保留在核中的不同类别的RNA分子，例如U3 snoRNA和U6 snRNA，也会响应Rev而输出到细胞质。与Rev介导的含有RRE的RNA的输出在机制上不同于加工的细胞mRNA的输出的概念一致，其中其NES被hnRNP A1的NES取代的嵌合Rev蛋白不诱导Rev响应性的输出mRNA，最后，我们证明 Rev/RRE 激活的 RNA 输出与其他核输出途径一样，与 Ran-GTPase 循环相关。
The human immunodeficiency virus type-1 Rev protein induces the nuclear export of intron-containing viral mRNAs that harbor its binding site, the Rev response element (RRE), A leucine-rich region of Rev, the activation domain, is essential for function and has been shown to be a nuclear export signal (NES), Although Rev exports viral RNAs that resemble cellular mRNAs, competition studies performed using microinjected Xenopus laevis oocytes have previously indicated that Rev utilizes a non-mRNA export pathway, Here, we show that Rev is able to induce the export of both spliceable and non-spliceable RRE-containing pre-mRNAs and that this activity is not dependent on the location of the RRE within the RNA. Importantly, even RNA molecules of different classes, such as U3 snoRNA and U6 snRNA, which are retained in the nucleus by non-pre-mRNA mechanisms, are exported to the cytoplasm in response to Rev, Consistent with the notion that Rev-mediated export of RRE-containing RNA is mechanistically distinct from the export of processed cellular mRNA, a chimeric Rev protein in which its NES is replaced by the NES of hnRNP Al does not induce the export of a Rev-responsive mRNA, Finally, we demonstrate that Rev/RRE-activated RNA export is, like other nuclear export pathways, linked to the Ran-GTPase cycle.