Concerted action of two 3' cap-independent translation enhancers increases the competitive strength of translated viral genomes.
Concerted action of two 3' cap-independent translation enhancers increases the competitive strength of translated viral genomes.
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DOI：
10.1093/nar/gkx643
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发表时间：
2017-09-19
影响因子：
14.9
通讯作者：
Simon AE
中科院分区：
文献类型：
--
作者：
Du Z;Alekhina OM;Vassilenko KS;Simon AE
几个植物病毒家族在其基因组(G)RNA的3‘非翻译区进化出不依赖帽子的翻译增强子(3’Cite)，以与细胞中正在进行的帽子依赖的翻译竞争。UmbraVirus豌豆花叶病毒(PEMV)2是唯一三个3‘端CITE增强翻译的例子：在不同属的病毒中发现了eIF4E结合的Panicum花叶病毒样翻译增强子(PTE)和核糖体结合的3’T型结构(TSS)，而与5‘端提供长距离相互作用的核糖体结合的KL-TSS是独一无二的。我们报道PTE是关键的翻译促进元件，但在没有KL-TSS的情况下，PTE通过隔离起始因子eIF4G抑制顺式和反式翻译。PEMV2在翻译方面强于细胞内模拟的mRNA，表明KL-TSS和PTE的结合是高效的。将3‘-5’相互作用从KL-TSS转移到PTE(以完成在其他病毒中发现的功能)支持体外翻译，但在没有KL-TSS的情况下，gRNA不能在原生质体中积累到可检测到的水平。结果表明，PTE与KL-TSS联合使用对翻译起始率没有明显影响，但增加了可供翻译的gRNA数量。提出了一个模型来解释3‘CITE对核糖体招募的调节如何增强病毒的适应性。
Several families of plant viruses evolved cap-independent translation enhancers (3′CITE) in the 3′ untranslated regions of their genomic (g)RNAs to compete with ongoing cap-dependent translation of cellular mRNAs. Umbravirus Pea enation mosaic virus (PEMV)2 is the only example where three 3′CITEs enhance translation: the eIF4E-binding Panicum mosaic virus-like translational enhancer (PTE) and ribosome-binding 3′ T-shaped structure (TSS) have been found in viruses of different genera, while the ribosome-binding kl-TSS that provides a long-distance interaction with the 5′ end is unique. We report that the PTE is the key translation promoting element, but inhibits translation in cis and in trans in the absence of the kl-TSS by sequestering initiation factor eIF4G. PEMV2 strongly outcompeted a cellular mRNA mimic for translation, indicating that the combination of kl-TSS and PTE is highly efficient. Transferring the 3′–5′ interaction from the kl-TSS to the PTE (to fulfill its functionality as found in other viruses) supported translationin vitro, but gRNA did not accumulate to detectable levels in protoplasts in the absence of the kl-TSS. It was shown that the PTE in conjunction with the kl-TSS did not markedly affect the translation initiation rate but rather increased the number of gRNAs available for translation. A model is proposed to explain how 3′CITE-based regulation of ribosome recruitment enhances virus fitness.
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