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，它们共同构成生命所需的功能构件。最初认为蛋白质表达主要受转录为特定 mRNA 的 DNA 数量控制。然而我们现在知道，高表达的 mRNA 有时很难翻译成蛋白质，而低表达的 mRNA 可以大量合成。因此，控制 mRNA 翻译的因素在调整/调节不同 mRNA 合成的蛋白质数量方面发挥着至关重要的作用。因此，翻译控制对关键的细胞功能有很大的贡献，例如增殖、生长和代谢，以及对营养缺乏或病原性病毒感染造成的压力做出有效的反应。 先前对细胞对病毒感染反应的分析主要评估了总 mRNA 含量（DNA 转录）。这导致了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）在压力下的积极作用，我们建议检查当细胞被不同RNA和DNA病毒家族（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，特定的mRNA主动翻译成蛋白质。我们的核糖体分析数据揭示了感染期间在翻译水平上受到调节的许多有趣的转录本。目前的研究计划旨在表征翻译机制控制的RNA及其在宿主-病原体相互作用中的功能。我们还旨在剖析所涉及的细胞内信号，并结合生化、分子生物学和遗传实验方法，评估翻译控制机制和顺式作用元件。我们的数据将揭示翻译控制机制在应对病毒感染方面的重要性，并确定翻译调节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.