Du Zhiyou, Alekhina Olga M, Vassilenko Konstantin S, Simon Anne E
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia.
Nucleic Acids Res. 2017 Sep 19;45(16):9558-9572. doi: 10.1093/nar/gkx643.
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.
几个植物病毒家族在其基因组（g）RNA的3'非翻译区进化出了不依赖帽的翻译增强子（3'CITE），以与细胞mRNA正在进行的依赖帽的翻译竞争。绒毛病毒豌豆耳突花叶病毒（PEMV）2是唯一一种有三个3'CITE增强翻译的例子：在不同属的病毒中发现了与真核起始因子4E（eIF4E）结合的类黍花叶病毒翻译增强子（PTE）和核糖体结合的3'T形结构（TSS），而能与5'端进行长距离相互作用的核糖体结合的kl-TSS是独一无二的。我们报告称，PTE是关键的翻译促进元件，但在没有kl-TSS的情况下，通过隔离起始因子eIF4G，它会顺式和反式抑制翻译。PEMV2在翻译过程中强烈胜过细胞mRNA模拟物，这表明kl-TSS和PTE的组合效率极高。将3'-5'相互作用从kl-TSS转移到PTE（以实现其在其他病毒中发现的功能）在体外支持翻译，但在没有kl-TSS的情况下，原生质体中的gRNA没有积累到可检测的水平。结果表明，PTE与kl-TSS结合并没有显著影响翻译起始速率，而是增加了可用于翻译的gRNA数量。本文提出了一个模型来解释基于3'CITE的核糖体招募调控如何提高病毒适应性。
