Molecular mechanisms of translation control during viral infection

遗传信息的流动始于DNA被转录成许多不同的信使RNA（mRNA）。然后，mRNA被翻译成特定的蛋白质，这些蛋白质共同构成了生命所需的功能性构建模块。蛋白质表达最初被认为主要由多少DNA转录成特定的mRNA来控制。然而，我们现在知道，高表达的mRNA有时会被微弱地翻译成蛋白质，而低表达的mRNA可以被大量合成。因此，控制mRNA翻译的因子在调节/调节由不同mRNA合成的蛋白质的量方面起着至关重要的作用。因此，翻译控制对关键的细胞功能，如增殖、生长和代谢，以及对营养缺乏或病原性病毒感染的应激的有效反应有很大贡献。 先前对病毒感染的细胞反应的分析主要评估总mRNA含量（DNA转录）。这导致在感染期间在转录水平上调节的多种抗病毒宿主因子的鉴定。鉴于蛋白质合成机制（mRNA翻译）在应激下的积极作用，我们已经提出，当细胞被不同家族的RNA和DNA病毒（呼肠孤病毒科，弹状病毒科，疱疹病毒科和痘病毒科）的病毒模型感染时，检查主动翻译成蛋白质的特定mRNA。我们的核糖体分析数据揭示了一些有趣的转录调控在感染过程中的翻译水平。目前的研究计划旨在表征由翻译机制控制的RNA及其在宿主-病原体相互作用中的功能。我们的目标还在于剖析所涉及的细胞内信号，并使用生物化学、分子生物学和遗传实验方法的组合，评估翻译控制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中的重要性，并确定翻译调节因子是否可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.