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

除了储存遗传信息外，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。锤头状核酶是一种引人注目的RNA，它具有非常有效地自我切割的催化能力。我们最近在不同类型的生物体中发现了许多锤头状核酶，包括人类、古细菌、细菌和许多DNA病毒。在这些物种中，核酶的功能明显不同于最初发现的植物RNA病毒中的已知功能，但这种功能现在仍然是一个谜。然而，我们有迹象表明，一些新型锤头状核酶对特定类型的金属敏感，允许细菌或病毒检测有毒金属，以适应恶劣的环境。此外，这种核酶存在于细菌中的事实为研究其生物学功能提供了理想的模式生物。通过对锤头状核酶的遗传学、生物化学和生物信息学的研究，将有助于我们对金属抗性和原核生物病毒的生物学研究。使用有针对性的计算搜索，我们将发现锤头状核酶更有可能具有调节作用。利用生物化学工具，我们将研究一些已知依赖于金属离子浓度的锤头状核酶和其他怀疑具有与金属离子传感相关的调节作用的核酶。基于计算机模拟的研究将与一种新的筛选技术相补充，以发现参与金属传感的其他非编码RNA。最近的研究表明，非编码RNA可能用作抗生素靶标，这证实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用途，以改善细菌工业用途中基因表达的调节。

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.