Ricci Emiliano P, Mure Fabrice, Gruffat Henri, Decimo Didier, Medina-Palazon Cahora, Ohlmann Théophile, Manet Evelyne
INSERM U758, Unité de Virologie Humaine, Ecole Normale Supérieure de Lyon, Lyon F-69007, France.
Nucleic Acids Res. 2009 Aug;37(15):4932-43. doi: 10.1093/nar/gkp497. Epub 2009 Jun 15.
The Epstein-Barr virus protein (EB2) allows the nuclear export of a particular subset of early and late viral RNAs derived from intronless genes. EB2 is conserved among most herpesvirus members and its presence is essential for the production of infectious particles. Here we show that, besides its role as a nuclear export factor, EB2 strongly stimulates translation of unspliced mRNAs without affecting overall cellular translation. Interestingly, this effect can be reversed by the addition of an intron within the gene. The spliced mRNA is then efficiently exported and translated even in the absence of EB2. Moreover, we show that EB2 associates with translating ribosomes and increases the proportion of its target RNA in the polyribosomal fraction. Finally, testing of EB2 homolog proteins derived from EBV-related herpesviruses, shows that, even if they play similar roles within the replication cycle of their respective virus, their mechanisms of action are different.
爱泼斯坦-巴尔病毒蛋白(EB2)可使源自无内含子基因的特定早期和晚期病毒RNA进行核输出。EB2在大多数疱疹病毒成员中保守,其存在对于感染性颗粒的产生至关重要。我们在此表明,除了作为核输出因子的作用外,EB2还强烈刺激未剪接mRNA的翻译,而不影响整体细胞翻译。有趣的是,通过在基因内添加内含子,这种效应可以逆转。然后,即使在没有EB2的情况下,剪接后的mRNA也能有效输出并翻译。此外,我们表明EB2与正在翻译的核糖体结合,并增加其靶RNA在多核糖体组分中的比例。最后,对源自与EBV相关的疱疹病毒的EB2同源蛋白进行测试表明,即使它们在各自病毒的复制周期中发挥类似作用,但其作用机制也不同。