Translation driven by an eIF4G core domain in vivo
Translation driven by an eIF4G core domain in vivo
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DOI：
10.1093/emboj/18.17.4865
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发表时间：
1999-09-01
期刊：
影响因子：
11.4
通讯作者：
Hentze, MW
中科院分区：
文献类型：
--
作者：
De Gregorio, E;Preiss, T;Hentze, MW
大多数真核生物mRNA具有5'端帽结构（m（7）GpppN）和3'端poly（A）尾，其分别通过结合真核生物翻译起始因子（eIF）4 E和poly（A）结合蛋白（PABP）来促进翻译起始。eIF 4G可以桥接eIF 4 E和PABP，并通过eIF 3与核糖体小亚基建立联系。我们将缺乏eIF 4 E-和PABP-结合位点的人eIF 4GI的C-末端区域与IRE结合蛋白IRP-1融合。这种嵌合蛋白足以在体内指导携带IRE的双顺反子mRNA的下游顺反子在其顺反子间空间的翻译。即使当通过5'端的翻译被抑制时，该功能也被保留。缺失分析将eIF 4G的保守中心结构域（氨基酸642-1091）定义为自主的“核糖体募集核心”，并暗示eIF 4A为关键结合伴侣。我们的数据揭示了保守的eIF 4G核糖体募集核心足以驱动活细胞中的生产性mRNA翻译。eIF 4G的C-末端三分之一是cDNA 3，并且可以充当调节域。
Most eukaryotic mRNAs possess a 5' cap structure (m(7)GpppN) and a 3' poly(A) tail which promote translation initiation by binding the eukaryotic translation initiation factor (eIF)4E and the poly(A) binding protein (PABP), respectively. eIF4G can bridge between eIF4E and PABP, and-through eIF3-is thought to establish a link to the small ribosomal subunit. We fused the C-terminal region of human eIF4GI lacking both the eIF4E- and PABP-binding sites, to the IRE binding protein IRP-1, This chimeric protein suffices to direct the translation of the downstream cistron of bicistronic mRNAs bearing IREs in their intercistronic space in vivo. This function is preserved even when translation via the 5' end is inhibited. Deletion analysis defined the conserved central domain (amino acids 642-1091) of eIF4G as an autonomous 'ribosome recruitment core' and implicated eIF4A as a critical binding partner. Our data reveal the sufficiency of the conserved eIF4G ribosome recruitment core to drive productive mRNA translation in living cells. The C-terminal third of eIF4G is dispensable, and may serve as a regulatory domain.