CRM1-dependent function of a cis-acting RNA export element
CRM1-dependent function of a cis-acting RNA export element
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DOI：
10.1128/mcb.22.7.2057-2067.2002
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发表时间：
2002-04-01
影响因子：
5.3
通讯作者：
Hope, TJ
中科院分区：
文献类型：
--
作者：
Popa, I;Harris, ME;Hope, TJ
病毒通常含有顺式作用RNA元件，其促进转录后加工和其信息的输出。这些元件分为两类，区别在于病毒或细胞RNA结合蛋白的存在。迄今为止，研究表明，病毒蛋白利用CRM 1依赖性输出途径，而细胞因子通常以CRM 1非依赖性方式发挥作用。在土拨鼠肝炎病毒（WHV）中发现的顺式作用元件（WHV转录后调节元件[WPRE]）具有转录后刺激转基因表达的能力，并且不需要病毒蛋白来发挥作用。传统观点认为，WPRE将以独立于CRM 1的方式发挥作用。然而，我们对该元件的研究表明，其有效功能对CAN/Nup 214的C末端的过表达和用抗微生物剂来普霉素B处理敏感。此外，CRM 1的过表达刺激WPRE活性。这些结果表明CRM 1在WPRE的出口功能中的直接作用。这一观察结果表明，WPRE是指导信息进入CRM 1依赖的mRNA输出途径在体细胞哺乳动物细胞。
Viruses often contain cis-acting RNA elements, which facilitate the posttranscriptional processing and export of their messages. These elements fall into two classes distinguished by the presence of either viral or cellular RNA binding proteins. To date, studies have indicated that the viral proteins utilize the CRM1-dependent export pathway, while the cellular factors generally function in a CRM1-independent manner. The cis-acting element found in the woodchuck hepatitis virus (WHV) (the WHV posttranscriptional regulatory element [WPRE]) has the ability to posttranscriptionally stimulate transgene expression and requires no viral proteins to function. Conventional wisdom suggests that the WPRE would function in a CRM1-independent manner. However, our studies on this element reveal that its efficient function is sensitive to the overexpression of the C terminus of CAN/Nup214 and treatment with the antimicrobial agent leptomycin B. Furthermore, the overexpression of CRM1 stimulates WPRE activity. These results suggest a direct role for CRM1 in the export function of the WPRE. This observation suggests that the WPRE is directing messages into a CRM1-dependent mRNA export pathway in somatic mammalian cells.