Non-coding RNA function and cations: studying the biological roles of the hammerhead ribozyme

非编码RNA功能和阳离子：研究锤头核酶的生物学作用

• 批准号: 418240-2012
• 负责人: Perreault, Jonathan
• 金额: $ 2.4万
• 依托单位: Institut national de la recherche scientifique
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629972
• 关键词: Non; coding; RNA; function; cations

Aside from storing hereditary information, DNA and RNA are now known to have many more functions. Living organisms have a plethora of RNAs that control numerous processes in cells. A remarkable RNA, the hammerhead ribozyme, has a catalytic ability to self-cleave very efficiently. We recently discovered numerous hammerhead ribozymes in diverse types of organisms, including humans, archaea, bacteria and many DNA-viruses. In these species, the ribozyme's function is clearly different from the one known in plant RNA-viruses where it was discovered initially, but this function remains a mystery for now. However, we have indications that some of the novel hammerhead ribozymes are sensitive to specific types of metals, allowing bacteria or viruses to detect toxic metals in order to adapt to a hostile environment. In addition, the fact that this ribozyme is found in bacteria provides ideal model organisms to study its biological function. Through genetic, biochemical and bioinformatics studies of the hammerhead ribozyme, we will get a better understanding of the biology of metal resistance and phages (viruses of prokaryotes). Using targeted computational searches, we will uncover hammerhead ribozymes more likely to have regulatory roles. With biochemical tools, we will study some hammerhead ribozymes known to depend on metal ion concentration and others suspected to have regulatory roles related to metal ion sensing. In silico based investigation will be complemented with a novel screening technique to find other non-coding RNAs involved in metal sensing. Recent studies showing the possible use of non-coding RNAs as antibiotic targets exemplifies tangible applications for these discoveries. The high potential of non-coding RNAs is also applicable to their use in genetic engineering to improve regulation of gene expression in industrial use of bacteria.

除了储存遗传信息，DNA和RNA现在已知还有更多的功能。生物体有大量的rna控制着细胞中的许多过程。一种非凡的RNA，锤头核酶，具有非常有效的自裂催化能力。我们最近在不同类型的生物体中发现了许多锤头核酶，包括人类、古生菌、细菌和许多dna病毒。在这些物种中，核酶的功能与最初在植物rna病毒中发现的核酶明显不同，但这种功能目前仍是一个谜。然而，我们有迹象表明，一些新的锤头核酶对特定类型的金属敏感，使细菌或病毒能够检测有毒金属，以适应恶劣的环境。此外，这种核酶在细菌中发现的事实为研究其生物学功能提供了理想的模式生物。通过对锤头核酶的遗传、生化和生物信息学研究，我们将更好地了解金属抗性和噬菌体（原核生物病毒）的生物学。使用有针对性的计算搜索，我们将发现锤头核酶更可能具有调节作用。利用生化工具，我们将研究一些已知依赖于金属离子浓度的锤头核酶和其他被怀疑具有与金属离子感应相关的调节作用的锤头核酶。以硅为基础的研究将辅以一种新的筛选技术，以寻找参与金属传感的其他非编码rna。最近的研究表明，可能使用非编码rna作为抗生素靶点例证了这些发现的实际应用。非编码rna的高潜力也适用于它们在基因工程中的应用，以改善细菌工业应用中基因表达的调控。