Poly(A)-binding protein binds to the non-polyadenylated 3′ untranslated region of dengue virus and modulates translation efficiency
Poly(A)-binding protein binds to the non-polyadenylated 3′ untranslated region of dengue virus and modulates translation efficiency
复制标题
DOI：
10.1099/vir.0.007021-0
复制
发表时间：
2009-03-01
影响因子：
3.8
通讯作者：
Harris, Eva
中科院分区：
文献类型：
--
作者：
Polacek, Charlotta;Friebe, Peter;Harris, Eva
多聚腺苷酸结合蛋白（PABP）是mRNA环化和多聚腺苷酸化mRNA翻译起始的关键分子。它同时结合mRNA的3' poly（A）尾和真核起始因子4G（eIF 4G），eIF 4G形成在5'端组装的翻译起始复合物的一部分，从而使RNA分子环化并增强翻译起始。在这里，我们报告了PABP与登革病毒（DENV）RNA的非多聚腺苷酸化3 '末端的结合。PABP在内部结合DENV 3'非翻译区（3' UTR），在两个哑铃结构附近的保守的3 '茎环的上游，并且可以被多聚（A）RNA置换。PABP特异性翻译抑制剂PABP相互作用蛋白2（Paip 2）干扰DENV 3 'UTR-PABP相互作用，并且Paip 2以剂量依赖性方式抑制幼仓鼠肾细胞提取物中DENV报告RNA的体外翻译。我们的研究结果显示了PABP的扩展翻译机制，与缺乏末端poly（A）尾的病毒RNA结合。
Poly(A)-binding protein (PABP) is a key player in mRNA circularization and translation initiation of polyadenylated mRNAs. It simultaneously binds the 3' poly(A) tail of an mRNA and eukaryotic initiation factor 4G (eIF4G), which forms part of the translation initiation complex assembling at the 5'end, thus circularizing the RNA molecule and enhancing translation initiation. Here, we report the binding of PABP to the non-polyadenylated 3'end of dengue virus (DENV) RNA. PABP binds the DENV 3' untranslated region (3'UTR) internally, upstream of the conserved 3'stem-loop near the two dumb-bell structures, and can be displaced by poly(A) RNA. The PABP-specific translation inhibitor PABP-interacting protein 2 (Paip2) interferes with the DENV 3'UTR-PABP interaction, and in vitro translation of DENV reporter RNAs in baby hamster kidney cell extracts is inhibited by Paip2 in a dose-dependent manner. Our findings show an expanded translation mechanism for PABP, binding to a viral RNA lacking a terminal poly(A) tail.