A virus-induced specialised ribosome

核糖体是存在于所有细胞生物体中的复杂分子机器。它们负责将信使RNA(MRNA)中的指令转化为组成蛋白质的氨基酸链，从而产生蛋白质。真核生物核糖体由两个亚基组成，分别称为60S和40S，它们由核糖体RNA和多个(~80)核糖体蛋白组成。在细胞中制造核糖体的过程是高度复杂和协调的，需要大量额外的核糖体组装因子，这些因素在其生产中具有特定的作用。长期以来，人们认为细胞中的所有核糖体都是相同的，在蛋白质生产中发挥关键作用，但对控制这一过程的影响很小。然而，新出现的证据表明，核糖体的亚群可能存在，它可以控制哪些mRNAs被翻译成蛋白质。这些所谓的特化核糖体可能在细胞内具有基本的调节功能。现在的一个主要问题是如何在细胞中产生特定的核糖体亚群，一种可能性是组成40S和60S亚基的核糖体蛋白的组成可能会改变，从而改变这些核糖体的调节功能或特异性。我们有令人兴奋的初步数据表明，病毒已经进化出控制受感染细胞中核糖体产生的方法。这将产生一个由病毒诱导的特殊核糖体，它可以控制病毒甚至细胞内mRNAs在受感染细胞中的翻译方式，促进病毒复制和病毒粒子的产生。我们已经证明，在疱疹病毒感染期间，一些核糖体蛋白被阻止参与产生40S和60S亚基，而其他核糖体蛋白水平增加。这表明核糖体蛋白的组成在感染过程中可能会发生变化。此外，我们还确定了一种病毒蛋白和如何在受感染细胞中实现这一目标的新机制。我们现在的目标是进一步研究这些观察结果，并确定病毒对核糖体生物发生的操纵对受感染细胞中专门的核糖体的组成有什么影响，以及这些变化如何影响使用一种称为核糖体图谱的全球方法来翻译细胞和病毒的mRNAs。此外，我们还将研究改变核糖体的组成对病毒复制周期的影响。此外，我们将评估产生这些病毒诱导的特化核糖体所需的基本病毒-宿主细胞相互作用，这可能为生产针对这一重要病原体家族的新型抗病毒试剂提供新的策略。

Ribosomes are complex molecular machines present in all cellular organisms. They are responsible for producing proteins by converting the instructions found in messenger RNA (mRNA) into the chains of amino-acids that make up proteins. Eukaryotic ribosomes are composed of two subunits, termed 60S and 40S, which are composed of ribosomal RNAs and multiple (~80) ribosomal proteins. The process to make ribosomes in the cell is highly complex and coordinated requiring lots of additional ribosome assembly factors which have specific roles in their production.It has long been thought that all ribosomes in the cell are the same, playing a critical role in protein production but having little influence on controlling the process. However, emerging evidence suggests that subpopulations of ribosomes may exist, which can control which mRNAs are translated into proteins. These so called specialised ribosomes could have fundamental regulatory functions within the cell. A major question now relates to how a subpopulation of specialised ribosomes could be produced in a cell and one possibility is that the composition of ribosomal proteins which make up the 40S and 60S subunits could be altered, changing the regulatory function or specificity of these ribosomes.We have exciting preliminary data suggesting that viruses have evolved ways to control the production of ribosomes in the infected cell. This would produce a virus-induced specialised ribosome which could control how viral and perhaps cellular mRNAs are translated in infected cells, enhancing virus replication and virion production. We have demonstrated that during herpesvirus infection, some ribosomal proteins are prevented from being involved in producing 40S and 60S subunits, whilst other ribosomal protein levels are increased. This suggests that the composition of ribosomal proteins may be altered during infection. In addition, we have identified a viral protein and novel mechanism of how this may be achieved in infected cells.We now aim to further investigate these observations and identify what effect viral manipulation of ribosome biogenesis has upon the composition of specialised ribosomes in infected cells and how these changes affect the translation of cellular and viral mRNAs using a global approach called ribosomal profiling. Moreover, we will investigate what effect altering the composition of ribosomes has upon the replication cycle of the virus. Furthermore, we will assess essential virus-host cell interactions which are required for the production of these viral-induced specialised ribosomes which may provide new strategies for the production of novel antiviral reagents for this important family of pathogens.