Studying novel protein biosynthesis genes.

研究新型蛋白质生物合成基因。

• 批准号: RGPIN-2014-04165
• 负责人: Golshani, Ashkan
• 金额: $ 3.86万
• 依托单位: Carleton University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=610871
• 关键词: Studying; novel; protein; biosynthesis; genes.

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.

基因表达调控的一个重要步骤是蛋白质合成水平。在蛋白质合成过程中，也称为翻译，嵌入mRNA分子中的遗传密码用于合成蛋白质，蛋白质负责大多数细胞功能。据估计，超过80%的原核细胞的能量用于合成蛋白质，突出了这一重要的细胞过程的重要性。许多医学上重要的抗生素也通过靶向翻译发挥其活性。翻译的缺失与癌症等重要的人类疾病有关。翻译控制用于在不同生理条件下调节多种mRNA的表达，例如胚胎发育和凋亡。几十年来，蛋白质合成及其控制一直是积极研究的主题，并且已经学到了很多东西。然而，影响蛋白质合成的基因和复杂途径的表征，以及其与其他细胞过程的交叉通信，需要更多的调查。在这里，我们建议研究新的影响，两种蛋白质，Bsc5和Mrh4，在真核模式生物酵母，酿酒酵母的翻译过程中。Bsc5蛋白似乎影响终止密码子识别。我们先前观察到BSC5基因的缺失增加了终止密码子旁路（通读）的频率。由于BSC5基因含有一个提前终止密码子，其调控基因表达的一种可能模式是通过绕过该提前终止密码子，其中Bsc5蛋白负性地自我调节其自身的表达。在此，我们建议进一步确认和研究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。我们以前的数据表明，它可能在含有抑制性二级结构的mRNA的翻译中发挥作用。在这里，我们建议进一步验证这一观察结果，并研究Mrh4蛋白可以影响蛋白质合成的机制。使用酵母菌株的功能丧失阵列，我们还计划研究可以影响具有抑制性二级结构的mRNA表达的其他基因。通过研究翻译过程，我们更好地理解了自然界蛋白质合成的统一原则，并获得了可用于医学应用的新策略，例如改进新的和改进的抗微生物化合物。