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The 5'-poly(A) leader of poxvirus mRNA confers a translational advantage that can be achieved in cells with impaired cap-dependent translation
PLoS Pathogens ( IF 6.7 ) Pub Date : 2017-08-30 , DOI: 10.1371/journal.ppat.1006602
Pragyesh Dhungel , Shuai Cao , Zhilong Yang

The poly(A) leader at the 5’-untranslated region (5’-UTR) is an unusually striking feature of all poxvirus mRNAs transcribed after viral DNA replication (post-replicative mRNAs). These poly(A) leaders are non-templated and of heterogeneous lengths; and their function during poxvirus infection remains a long-standing question. Here, we discovered that a 5’-poly(A) leader conferred a selective translational advantage to mRNA in poxvirus-infected cells. A constitutive and uninterrupted 5’-poly(A) leader with 12 residues was optimal. Because the most frequent lengths of the 5’-poly(A) leaders are 8–12 residues, the result suggests that the poly(A) leader has been evolutionarily optimized to boost poxvirus protein production. A 5’-poly(A) leader also could increase protein production in the bacteriophage T7 promoter-based expression system of vaccinia virus, the prototypic member of poxviruses. Interestingly, although vaccinia virus post-replicative mRNAs do have 5’- methylated guanosine caps and can use cap-dependent translation, in vaccinia virus-infected cells, mRNA with a 5’-poly(A) leader could also be efficiently translated in cells with impaired cap-dependent translation. However, the translation was not mediated through an internal ribosome entry site (IRES). These results point to a fundamental mechanism poxvirus uses to efficiently translate its post-replicative mRNAs.



中文翻译:

痘病毒mRNA的5'-poly(A)前导序列具有翻译优势,可以在受损的帽依赖性翻译细胞中实现

5'-非翻译区(5'-UTR)的poly(A)前导序列是病毒DNA复制后复制的所有痘病毒mRNA(复制后mRNA)的异常显着特征。这些poly(A)引物是非模板的,且长度不一。其在痘病毒感染期间的功能仍然是一个长期存在的问题。在这里,我们发现5'-poly(A)前导赋予痘病毒感染细胞中的mRNA选择性翻译优势。具有12个残基的组成性且不间断的5'-poly(A)前导序列是最佳的。由于5'-poly(A)前导序列最常见的长度是8-12个残基,因此该结果表明poly(A)前导序列经过进化优化以增强痘病毒蛋白的产生。一个5'-poly(A)的领导者还可以增加痘病毒的原型成员痘苗病毒基于噬菌体T7启动子的表达系统中的蛋白质产量。有趣的是,尽管痘苗病毒复制后的mRNA确实具有5'-甲基鸟嘌呤帽,并且可以使用依赖于帽的翻译,但是在痘苗病毒感染的细胞中,带有5'-poly(A)前导序列的mRNA也可以在细胞中有效翻译。依赖于上限的翻译功能受损。但是,翻译不是通过内部核糖体进入位点(IRES)介导的。这些结果表明痘病毒用于有效翻译其复制后mRNA的基本机制。在牛痘病毒感染的细胞中,带有5'-poly(A)前导序列的mRNA也可以在受损的帽依赖性翻译中被有效地翻译。但是,翻译不是通过内部核糖体进入位点(IRES)介导的。这些结果表明痘病毒用于有效翻译其复制后mRNA的基本机制。在牛痘病毒感染的细胞中,带有5'-poly(A)前导序列的mRNA也可以在受损的帽依赖性翻译中被有效地翻译。但是,翻译不是通过内部核糖体进入位点(IRES)介导的。这些结果表明痘病毒用于有效翻译其复制后mRNA的基本机制。

更新日期:2017-09-14
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