Molecular dissection of the eukaryotic initiation factor 4E (eIF4E) export-competent RNP
Molecular dissection of the eukaryotic initiation factor 4E (eIF4E) export-competent RNP
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DOI：
10.1038/emboj.2009.53
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发表时间：
2009-04-22
期刊：
影响因子：
11.4
通讯作者：
Borden, Katherine L. B.
中科院分区：
文献类型：
--
作者：
Topisirovic, Ivan;Siddiqui, Nadeem;Borden, Katherine L. B.
真核翻译起始因子 4E (eIF4E) 通过影响 mRNA 输出和帽依赖性翻译来控制基因表达，这两者都有助于其致癌潜力。与其翻译功能相反，eIF4E 的 mRNA 输出功能知之甚少。使用 RNP 分离/质谱方法，我们鉴定了 eIF4E mRNA 输出的候选辅助因子，包括 LRPPRC。该蛋白与含有 eIF4E 敏感元件 (4E-SE) 的 mRNA 结合，其过度表达会改变几种 eIF4E 敏感 mRNA 的核输出。 LRPPRC 介导的 eIF4E mRNA 输出功能的改变需要其 eIF4E 结合位点的完整性，并且它与 eIF4E 的亚细胞重新分布相一致。 eIF4E 输出 RNP 在组成上与批量 mRNA 输出途径不同，因为 eIF4E 和 eIF4E 敏感 mRNA 不与一般 mRNA 输出因子（例如 TAP/NXF1 或 REF/Aly）相关。我们的数据表明，mRNA 输出途径已经进化为特定 mRNA，通过在输出水平调节基因组的表达来实现生化途径的差异调节。
The eukaryotic translation initiation factor 4E (eIF4E) controls gene expression through its effects on mRNA export and cap-dependent translation, both of which contribute to its oncogenic potential. In contrast to its translation function, the mRNA export function of eIF4E is poorly understood. Using an RNP isolation/mass spectrometry approach, we identified candidate cofactors of eIF4E mRNA export including LRPPRC. This protein associates with mRNAs containing the eIF4E-sensitivity element (4E-SE), and its overexpression alters the nuclear export of several eIF4E-sensitive mRNAs. LRPPRC-mediated alteration of eIF4E's mRNA export function requires the integrity of its eIF4E-binding site and it coincides with the subcellular re-distribution of eIF4E. The eIF4E export RNP is distinct in composition from the bulk mRNA export pathway, in that eIF4E- and eIF4E- sensitive mRNAs do not associate with general mRNA export factors such as TAP/NXF1 or REF/Aly. Our data indicate that mRNA export pathways have evolved for specific mRNAs enabling the differential regulation of biochemical pathways by modulating the expression of groups of genes at the level of their export.