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Abstract：
The eukaryotic translation initiation factor eIF4E acts as a multifunctional factor that simultaneously influences mRNA processing, export, and translation in many organisms. Its multifactorial effects are derived from its capacity to bind to the methyl-7-guanosine cap on the 5\'end of mRNAs and thus can act as a cap chaperone for transcripts in the nucleus and cytoplasm. In this review, we describe the multifactorial roles of eIF4E in major mRNA-processing events including capping, splicing, cleavage and polyadenylation, nuclear export and translation. We discuss the evidence that eIF4E acts at two levels to generate widescale changes to processing, export and ultimately the protein produced. First, eIF4E alters the production of components of the mRNA processing machinery, supporting a widescale reprogramming of multiple mRNA processing events. In this way, eIF4E can modulate mRNA processing without physically interacting with target transcripts. Second, eIF4E also physically interacts with both capped mRNAs and components of the RNA processing or translation machineries. Further, specific mRNAs are sensitive to eIF4E only in particular mRNA processing events. This selectivity is governed by the presence of cis-acting elements within mRNAs known as USER codes that recruit relevant co-factors engaging the appropriate machinery. In all, we describe the molecular bases for eIF4E\'s multifactorial function and relevant regulatory pathways, discuss the basis for selectivity, present a compendium of ~80 eIF4E-interacting factors which play roles in these activities and provide an overview of the relevance of its functions to its oncogenic potential. Finally, we summarize early-stage clinical studies targeting eIF4E in cancer.
摘要：
真核翻译起始因子eIF4E作为一个多功能因子，同时影响mRNA加工，export,以及在许多生物体中的翻译。它的多因素作用源于其与mRNAs5'末端的甲基-7-鸟苷帽结合的能力，因此可以充当细胞核和细胞质中转录物的帽伴侣。在这次审查中,我们描述了eIF4E在主要mRNA加工事件中的多因素作用，包括加帽，拼接,裂解和聚腺苷酸化，核出口和翻译。我们讨论的证据表明，eIF4E在两个层面上产生了对处理的大规模变化，出口和最终产生的蛋白质。首先,eIF4E改变了mRNA加工机械组件的生产，支持多个mRNA处理事件的大规模重编程。这样,eIF4E可以调节mRNA加工而不与靶转录物物理相互作用。第二,eIF4E还与加帽的mRNA和RNA加工或翻译机制的组分物理地相互作用。Further,特定mRNA仅在特定mRNA加工事件中对eIF4E敏感。这种选择性受被称为USER代码的mRNA内顺式作用元件的存在支配,所述mRNA招募参与适当机制的相关辅因子。总之,我们描述了eIF4E的多因素功能和相关调节途径的分子基础，讨论选择性的基础，提供约80个eIF4E相互作用因素的汇编，这些因素在这些活动中起作用，并概述其功能与其致癌潜力的相关性。最后,我们总结了针对eIF4E在癌症中的早期临床研究。
