Eukaryotic translation initiation factor 4E availability controls the switch between cap-dependent and internal ribosomal entry site-mediated translation
Eukaryotic translation initiation factor 4E availability controls the switch between cap-dependent and internal ribosomal entry site-mediated translation
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DOI：
10.1128/mcb.25.23.10556-10565.2005
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发表时间：
2005-12-01
影响因子：
5.3
通讯作者：
Sonenberg, N
中科院分区：
文献类型：
--
作者：
Svitkin, YV;Herdy, B;Sonenberg, N
通过真核翻译起始因子4F （eIF4F）将核糖体募集到mrna的5'端，从而启动m(7) g -cap -cap细胞mrna的翻译。eIF4F是一种异三聚体复合物，由帽结合亚基（eIF4E）和由支架分子（eIF4G）桥接的RNA解旋酶（eIF4A）组成。内部翻译起始不需要cap和eIF4E，发生在含有内部核糖体进入位点（IRESs）的病毒和细胞mrna上。在这里，我们证明了eIF4E的可用性在小核糖核酸病毒感染细胞中从帽依赖转换到ires介导的翻译中起着关键作用。当封顶mRNA和含ires mRNA同时存在时（如在完整细胞或体外翻译提取物中），与eIF4F复合物相关的eIF4E数量的减少会引起ires介导的病毒mRNA翻译的显著增加。这种效应在去除顶帽mrna的翻译提取物中没有观察到，这表明顶帽mrna与含ires的mrna竞争翻译。这些数据解释了许多报道的观察结果，其中病毒mrna在感染期间优先翻译。
Translation of m(7)G-capped cellular mRNAs is initiated by recruitment of ribosomes to the 5' end of mRNAs via eukaryotic translation initiation factor 4F (eIF4F), a heterotrimeric complex comprised of a cap-binding subunit (eIF4E) and an RNA helicase (eIF4A) bridged by a scaffolding molecule (eIF4G). Internal translation initiation bypasses the requirement for the cap and eIF4E and occurs on viral and cellular mRNAs containing internal ribosomal entry sites (IRESs). Here we demonstrate that eIF4E availability plays a critical role in the switch from cap-dependent to IRES-mediated translation in picornavirus-infected cells. When both capped and IRES-containing mRNAs are present (as in intact cells or in vitro translation extracts), a decrease in the amount of eIF4E associated with the eIF4F complex elicits a striking increase in IRES-mediated viral mRNA translation. This effect is not observed in translation extracts depleted of capped mRNAs, indicating that capped mRNAs compete with IRES-containing mRNAs for translation. These data explain numerous reported observations where viral mRNAs are preferentially translated during infection.