PABP1 and elF4Gl associate with influenza virus NS1 protein in viral mRNA translation initiation complexes
PABP1 and elF4Gl associate with influenza virus NS1 protein in viral mRNA translation initiation complexes
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DOI：
10.1099/vir.0.19487-0
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发表时间：
2003-12-01
影响因子：
3.8
通讯作者：
Nieto, A
中科院分区：
文献类型：
--
作者：
Burgui, I;Aragón, T;Nieto, A
此前已有研究表明，流感病毒NS1蛋白可促进病毒的翻译，但不能促进细胞内的mRNAs的翻译。这种增强是通过提高翻译起始率而发生的，并且需要所有病毒mRNAs共同的5‘UTR序列。与这些发现一致，我们在这里表明，在病毒感染期间，病毒mRNAs而不是细胞mRNAs与NS1相关。我们先前已经报道，NS1与翻译起始因子eIF4GI在其聚(A)结合蛋白1(PABP1)相互作用区域旁边相互作用，并且在流感病毒感染的细胞中NS1和eIF4GI相关。在这里，我们证明了NS1虽然能够结合Poly(A)，但不与PABP1竞争与eIF4GI的结合，此外，NS1和PABP1在体内和体外都以不依赖于RNA的方式相互作用。残基365与PABP1之间的相互作用以及NS1中残基1与81之间的相互作用图。这些图谱研究，加上之前报道的NS1-eIF4GI和PABP1-eIF4GI相互作用，表明这三种蛋白质的结合将是相容的。综上所述，这些和以前发表的数据表明，NS1与eIF4GI和PABP1以及与病毒mRNAs的相互作用可以促进43S复合体对病毒mRNAs的特异性招募。
It has previously been shown that influenza virus NS1 protein enhances the translation of viral but not cellular mRNAs. This enhancement occurs by increasing the rate of translation initiation and requires the 5'UTR sequence, common to all viral mRNAs. In agreement with these findings, we show here that viral mRNAs, but not cellular mRNAs, are associated with NS1 during virus infection. We have previously reported that NS1 interacts with the translation initiation factor eIF4GI, next to its poly(A)-binding protein 1 (PABP1)-interacting domain and that NS1 and eIF4GI are associated in influenza virus-infected cells. Here we show that NS1, although capable of binding poly(A), does not compete with PABP1 for association with eIF4GI and, furthermore, that NS1 and PABP1 interact both in vivo and in vitro in an RNA-independent manner. The interaction maps between residues 365 and 535 in PABP1 and between residues 1 and 81 in NS1. These mapping studies, together with those previously reported for NS1-eIF4GI and PABP1-eIF4GI interactions, imply that the binding of all three proteins would be compatible. Collectively, these and previously published data suggest that NS1 interactions with eIF4GI and PABP1, as well as with viral mRNAs, could promote the specific recruitment of 43S complexes to the viral mRNAs.