Structure and Function of Nucleic Acids

描述（由申请人提供）：长期目标是能够仅从其碱基序列推断出RNA分子的三维结构。小干扰rna和微rna帮助调控基因表达。信使RNA分子传递和解释DNA中的遗传信息以产生蛋白质。核糖体rna和转移rna是合成蛋白质所必需的机器的关键部分。RNA加工中的错误、信使RNA翻译的控制以及信使RNA寿命的控制与许多人类疾病有关，包括一些神经退行性疾病，如卢伽雷氏病。在RNA病毒中，RNA既是遗传信息，又是蛋白质合成的信使。因此，天然存在的rna和病毒rna是预防或治疗疾病的药物的突出靶点。到目前为止，绝大多数药物靶点都是蛋白质，因此RNA提供了重要的新机会。了解RNA的三维结构、稳定性和相互转换速率对于理解RNA的功能至关重要，也是开发抗RNA药物的关键。为了获得这方面的知识，RNA分子在实验室中通过RNA聚合酶从DNA模板合成。一个头附着在单个RNA分子的两端；一颗珠子放在微移液管中，另一颗放在激光阱中。通过移动微移液管，RNA分子展开，测量珠子之间的距离（纳米）和激光阱中珠子上的力（皮牛顿）。这些数据提供了折叠RNA（二级和三级结构）相对于未折叠单链的热力学稳定性。还测量了展开和再折叠的速率。这些信息将有助于提高对RNA结构、稳定性和动力学的理解。这将有助于理解RNA的功能，以及控制RNA在病毒和遗传疾病中的作用

DESCRIPTION (provided by applicant): The long term goal is to be able to deduce a three-dimensional structure for an RNA molecule solely from the sequence of its bases. Small interfering RNAs and micro RNAs help regulate gene expression. Messenger RNA molecules transfer and interpret the genetic information in DNA to produce proteins. Ribosomal RNAs and transfer RNAs are key parts of the machinery necessary to synthesize the proteins. Errors in RNA processing, in control of messenger RNA translation, and in control of messenger RNA lifetimes are linked to many human diseases, including several neurodegenerative diseaeses such as Lou Gehrig's disease. In RNA viruses, the RNA is both the genetic information, and the messenger for protein synthesis. Thus, naturally occurring RNAs and viral RNAs are outstanding targets for drugs to prevent or cure disease. The overwhelming majority of drug targets up to now have been proteins, so RNA provides major new opportunities. Knowledge of the three-dimensional structures of RNAs, their stabilities, and their rates of interconversion is crucial to understanding RNA function, and is key to developing anti-RNA drugs. In order to obtain this knowledge, RNA molecules are synthesized in the laboratory by RNA potymerase from a DNA template. A bead is attached to each end of a single RNA molecule; one bead is held in a micropipet, the other in a laser trap. By moving the micropipet, the RNA molecule is unfolded The distance (nanometers) between the beads and the force (piconewtons) on the bead in the laser trap is measured. These data provide the thermodynamic stabilities of the folded RNA (secondary and tertiary structures) relative to the unfolded single strand. The rates of unfolding and refolding are also measured. This information will lead to improved understanding of RNA structure, stability, and dynamics. It will help in understanding RNA function, and in controlling the role of RNA in viral and genetic diseases