Structural and functional analysis of the RNA transport element, a member of an extensive family present in the mouse genome.
Structural and functional analysis of the RNA transport element, a member of an extensive family present in the mouse genome.
复制标题
RNA 转运元件（小鼠基因组中存在的一个广泛家族的成员）的结构和功能分析。
DOI：
10.1128/jvi.79.4.2356-2365.2005
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发表时间：
2005
影响因子：
5.4
通讯作者：
Felber,BarbaraK
中科院分区：
文献类型：
--
作者：
Smulevitch,Sergey;Michalowski,Daniel;Zolotukhin,AndreiS;Schneider,Ralf;Bear,Jenifer;Roth,Patricia;Pavlakis,GeorgeN;Felber,BarbaraK
我们以前鉴定了一种RNA转运元件（RTE），存在于啮齿动物脑池内A颗粒逆转录元件的一个亚类中（F。纳皮河施耐德A. Zolotukhin，S. Smulevitch，D. Michalowski，J. Bear，B. Felber和G. Pavlakis，J.Virol.75：4558-4569，2001），其能够取代人免疫缺陷病毒1型中的Rev-应答元件调节。RTE指导的mRNA输出由一种仍然未知的细胞因子介导，不依赖于CRM 1核输出受体，并且在脊椎动物中是保守的。在这里，我们表明，这种RTE折叠成一个扩展的RNA二级结构，因此不像任何已知的RTE。计算机检索显示存在105个相同的元件和超过3,000个相关元件，这些元件与RTE共享至少70%的序列同一性，并且在所有小鼠染色体上发现。这些相关的元素被预测折叠成RTE样结构。序列和结构的比较表明，RTE和相关元件可以分为四组。RTE的突变显示，最小元件包含四个内部茎环，这是在哺乳动物细胞中不可缺少的功能。相比之下，只有部分元素是必不可少的，以介导RNA运输microinjectedXenopus laevisoocyte核。重要的是，能够促进RNA转运的最小RTE具有在所有RTE相关元件中保留的关键结构特征，进一步支持其功能重要性。因此，RTE功能取决于复杂的二级结构，其对于与细胞输出因子的相互作用是重要的。
We previously identified an RNA transport element (RTE), present in a subclass of rodent intracisternal A particle retroelements (F. Nappi, R. Schneider, A. Zolotukhin, S. Smulevitch, D. Michalowski, J. Bear, B. Felber, and G. Pavlakis, J. Virol.75:4558-4569, 2001), that is able to replace Rev-responsive element regulation in human immunodeficiency virus type 1. RTE-directed mRNA export is mediated by a still-unknown cellular factor(s), is independent of the CRM1 nuclear export receptor, and is conserved among vertebrates. Here we show that this RTE folds into an extended RNA secondary structure and thus does not resemble any known RTEs. Computer searches revealed the presence of 105 identical elements and more than 3,000 related elements which share at least 70% sequence identity with the RTE and which are found on all mouse chromosomes. These related elements are predicted to fold into RTE-like structures. Comparison of the sequences and structures revealed that the RTE and related elements can be divided into four groups. Mutagenesis of the RTE revealed that the minimal element contains four internal stem-loops, which are indispensable for function in mammalian cells. In contrast, only part of the element is essential to mediate RNA transport in microinjectedXenopus laevisoocyte nuclei. Importantly, the minimal RTE able to promote RNA transport has key structural features which are preserved in all the RTE-related elements, further supporting their functional importance. Therefore, RTE function depends on a complex secondary structure that is important for the interaction with the cellular export factor(s).