Molecular Virology group, Department of Medicine and Life Sciences, Universitat Pompeu Fabra, 08003, Barcelona, Spain.
Institute of Technology, University of Tartu, 50411, Tartu, Estonia.
Nat Commun. 2022 Aug 11;13(1):4725. doi: 10.1038/s41467-022-31835-x.
Ample evidence indicates that codon usage bias regulates gene expression. How viruses, such as the emerging mosquito-borne Chikungunya virus (CHIKV), express their genomes at high levels despite an enrichment in rare codons remains a puzzling question. Using ribosome footprinting, we analyze translational changes that occur upon CHIKV infection. We show that CHIKV infection induces codon-specific reprogramming of the host translation machinery to favor the translation of viral RNA genomes over host mRNAs with an otherwise optimal codon usage. This reprogramming was mostly apparent at the endoplasmic reticulum, where CHIKV RNAs show high ribosome occupancy. Mechanistically, it involves CHIKV-induced overexpression of KIAA1456, an enzyme that modifies the wobble U34 position in the anticodon of tRNAs, which is required for proper decoding of codons that are highly enriched in CHIKV RNAs. Our findings demonstrate an unprecedented interplay of viruses with the host tRNA epitranscriptome to adapt the host translation machinery to viral production.
大量证据表明密码子使用偏性调节基因表达。新兴的蚊媒传播的基孔肯雅病毒 (CHIKV) 等病毒尽管富含稀有密码子，但仍能高水平表达基因组，这仍然是一个令人费解的问题。我们使用核糖体足迹分析技术分析了 CHIKV 感染时发生的翻译变化。结果表明，CHIKV 感染诱导宿主翻译机制的密码子特异性重编程，以优先翻译病毒 RNA 基因组，而不是具有最佳密码子使用的宿主 mRNA。这种重编程在富含核糖体的内质网中最为明显。从机制上讲，它涉及 CHIKV 诱导的 KIAA1456 的过度表达，KIAA1456 是一种修饰 tRNA 反密码子中 wobble U34 位置的酶，对于正确解码在 CHIKV RNA 中高度富集的密码子至关重要。我们的研究结果表明，病毒与宿主 tRNA 表观转录组之间存在前所未有的相互作用，以适应宿主翻译机制来进行病毒的产生。
