Studying novel protein biosynthesis genes.

基因表达调控的一个重要步骤是在蛋白质合成水平。在蛋白质合成（也称为翻译）过程中，嵌入在mRNA分子中的遗传密码被用来合成蛋白质，这些蛋白质负责大多数细胞功能。据估计，原核细胞80%以上的能量用于合成蛋白质，这凸显了这一基本细胞过程的重要性。许多医学上重要的抗生素也通过靶向翻译发挥作用。翻译异常与癌症等重要的人类疾病有关。翻译控制用于调节多种mrna在不同生理条件下的表达，如胚胎发育和细胞凋亡。几十年来，蛋白质合成及其控制一直是人们积极研究的主题，人们已经了解了很多。然而，影响蛋白质合成的基因和复杂途径的表征，以及与其他细胞过程的交叉通讯，需要更多的研究。在此，我们拟研究Bsc5和Mrh4两种蛋白对真核模式生物酵母（Saccharomyces cerevisiae）翻译过程的新影响。Bsc5蛋白似乎影响终止密码子识别。我们之前观察到BSC5基因的缺失增加了终止密码子旁路的频率（读通）。由于BSC5基因含有一个过早停止密码子，BSC5蛋白调控基因表达的一种可能模式是通过绕过这个过早停止密码子，从而自我负性调节自身的表达。在此，我们拟进一步确认和研究Bsc5蛋白对蛋白质合成过程的影响。Mrh4蛋白被认为参与RNA分子的重塑。我们之前的数据表明，它可能在含有抑制二级结构的mrna的翻译中发挥作用。在此，我们建议进一步验证这一观察结果，并研究Mrh4蛋白影响蛋白质合成的机制。利用功能缺失的酵母菌株阵列，我们还计划研究其他可以影响具有抑制二级结构的mrna表达的基因。通过研究翻译过程，我们可以更好地理解自然界中蛋白质合成的统一原则，并推导出可用于医学应用的新策略，例如开发新的和改进的抗微生物化合物。

An important step in the regulation of gene expression is at the level of protein synthesis. During protein synthesis, also known as translation, the genetic codes embedded in mRNA molecules are used to synthesize proteins, which are responsible for the majority of cellular functions. It is estimated that more than 80% of a prokaryotic cell’s energy is spent on synthesizing proteins, highlighting the importance of this essential cellular process. Many medically important antibiotics also exert their activities by targeting translation. Abnormalities in translation have been linked to important human conditions such as cancer. Translation control is used to regulate the expression of a variety of mRNAs under different physiological conditions such as embryonic development and apoptosis. Protein synthesis and its control has been the subject of vigorous investigations over many decades and much has been learned. However, characterization of the genes and complex pathways that influence protein synthesis, as well as its cross communication with other cellular processes, requires more investigation. Here, we propose to study the novel influence of two proteins, Bsc5 and Mrh4, on the process of translation in the eukaryotic model organism yeast, Saccharomyces cerevisiae. Bsc5 protein appears to affect termination codon recognition. We previously observed that deletion of BSC5 gene increases the frequency of stop codon bypass (readthrough). Since BSC5 gene contains a premature stop codon, a possible mode of its regulation of gene expression is through the bypass of this premature stop codon where Bsc5 protein negatively self-regulates its own expression. Here, we propose to further confirm and investigate the influence of Bsc5 protein on the process of protein synthesis. Mrh4 protein is thought to be involved in remodeling of RNA molecules. Our previous data suggests that it may play a role in the translation of mRNAs that contain inhibitory secondary structures. Here, we propose to further validate this observation and to study the mechanism by which Mrh4 protein can affect protein synthesis. Using a loss-of-function array of yeast strains we also plan to study other genes that can influence the expression of mRNAs with inhibitory secondary structures. By studying the process of translation, we gain a better understanding of the unifying principles of protein synthesis in nature and derive novel strategies that could be used in medical applications, such as advancement of new and improved anti-microbial compounds.