Molecular mechanisms of translation control during viral infection

遗传信息流开始于DNA被转录成许多不同的信使RNA(MRNAs)。然后，mRNAs被翻译成特定的蛋白质，这些蛋白质共同构成生命所需的功能构件。蛋白质的表达最初被认为主要由多少DNA转录成特定的mRNAs来控制。然而，我们现在知道，高表达的mRNAs有时被微弱地翻译成蛋白质，而低表达的mRNAs可以被大量合成。因此，控制信使核糖核酸翻译的因素在调节不同信使核糖核酸合成的蛋白质数量方面起着至关重要的作用。因此，翻译控制极大地促进了关键的细胞功能，如增殖、生长和新陈代谢，以及对营养缺乏或病原性病毒感染的压力越来越有效的反应。 以前对细胞对病毒感染的反应的分析主要评估了总的mRNA含量(DNA转录)。这导致了在感染过程中在转录水平上调节的多种抗病毒宿主因子的识别。鉴于在应激状态下蛋白质合成机制(信使核糖核酸的翻译)的活跃作用，我们建议检测当细胞被不同家族的RNA和DNA病毒(呼肠孤病毒科、横纹病毒科、疱疹病毒科和痘病毒科)的病毒模型感染时主动翻译成蛋白质的特定mRNAs。我们的核糖体图谱数据显示，在感染过程中，有一些有趣的转录本在翻译水平上受到调控。目前的研究计划旨在描述由翻译机制控制的RNA及其在宿主-病原体相互作用中的功能。我们还打算分析涉及的细胞内信号，并结合生化、分子生物学和遗传学实验方法，评估翻译调控机制和顺式作用元件。我们的数据将阐明翻译控制机制在应对病毒感染方面的重要性，并确定翻译调控因子是否可以用于开发基于病毒的技术。

The flow of genetic information begins by DNA being transcribed into many different messenger RNAs (mRNAs). The mRNAs are then translated into specific proteins, which together comprise the functional building blocks required for life. Protein expression was originally thought to be primarily controlled by how much DNA is transcribed into specific mRNAs. However we now know that highly expressed mRNAs are sometimes weakly translated into proteins, while poorly expressed mRNAs can be synthesized abundantly. Therefore, the factors that control mRNA translation play a vital role in adjusting/regulating the amount of proteins synthesized from distinct mRNAs. Translation control thus strongly contributes to critical cellular functions, such as proliferation, growth, and metabolism, as well as mounting efficient responses to stresses from nutrient deprivation or pathogenic viral infections. Previous analyses of cellular response to viral infection have primarily assessed total mRNA content (DNA transcription). This has lead to the identification of multiple anti-viral host factors regulated at the transcription level during infection. In view of the active role of the protein synthesis machinery (mRNA translation) while under stress, we have proposed to examine the specific mRNAs actively translated into proteins when cells are infected with viral models of different families of RNA and DNA viruses (Reoviridae, Rhabdoviridae, Herpesviridae and Poxviridae). Our ribosome profiling data have revealed a number of interesting transcripts regulated at the translation level during infection. The current research program is designed to characterize the RNAs controlled by translation mechanisms and their functions in host-pathogen interactions. We also aim to dissect the intracellular signals involved, and using a combination of biochemical, molecular biology and genetic experimental approaches, assess translation control mechanisms and cis-acting elements. Our data will shed light on the importance of translational control mechanisms in response to viral infection and establish whether regulators of translation could be utilized in the development of viral-based technologies.