Structure and Function of Nucleic Acids

描述（由申请人提供）：长期目标是能够从其序列中正确预测(1)RNA如何折叠成其生物功能形式，(2)其结构如何影响其功能，以及(3)其折叠速度和对环境中蛋白质和其他配体的反应速度。RNA分子在基因表达的各个方面都是至关重要的。信使rna在DNA中传递遗传信息；在RNA病毒中，RNA既是遗传信息，又是蛋白质合成的信使。非编码RNA，包括微小RNA和小干扰RNA，调节DNA转录成RNA和RNA翻译成蛋白质。信使rna的加工和控制错误与人类疾病有关，包括神经退行性疾病，如卢伽雷氏病。人们正在研究rna作为信使rna的抑制剂来沉默特定基因和治疗疾病。人类和病毒的rna也是预防或治疗人类疾病的药物的突出靶点。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RNA作为药物和药物靶点的关键。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。一个微米大小的珠子被连接到单个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。测量了激光阱中珠子之间的距离（纳米）和珠子上的力（皮牛顿）。这些数据提供了RNA的热力学稳定性及其展开和再折叠的速率。解开、转录和翻译RNA的蛋白质以及抑制这些过程的药物的作用是确定的。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在人类疾病中的作用。RNA病毒引起许多人类疾病，包括艾滋病、流感、丙型肝炎、SARS等。在人类体内自然发生的rna故障也会导致疾病。对RNA结构的研究将有助于更好地了解RNA的功能，并有助于开发更好的药物来治疗或预防人类疾病。

DESCRIPTION (provided by applicant): The long term goal is to be able to correctly predict from its sequence (1) how an RNA folds into its biologically functional form, (2) how its structure affects its function, and (3) how fast it folds and responds to proteins and other ligands in its environment. RNA molecules are crucial in all aspects of gene expression. Messenger RNAs transfer the genetic information in DNA; in RNA viruses the RNA is both the genetic information, and the messenger for protein synthesis. Non-coding RNAs, including microRNAs and small interfering RNAs, regulate transcription of DNA to RNA and translation of RNA to protein. Errors in processing and control of messenger RNAs are linked to human diseases, including neurodegenerative diseases such as Lou Gehrig's disease. RNAs are being investigated as inhibitors of messenger RNAs to silence specific genes, and to cure diseases. RNAs both human and viral are also outstanding targets for drugs to prevent or cure human diseases. 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 RNA as drugs and as targets for drugs. In order to obtain this knowledge, RNA molecules are synthesized in the laboratory by RNA polymerase from a DNA template. A micron-sized bead is attached to each end of a single RNA molecule; one bead is held in a micropipette, the other in a laser trap. By moving the micropipette, the RNA molecule is unfolded. The distance (nanometers) between the beads and the force (piconewtons) on the bead in the laser trap are measured. These data provide the thermodynamic stability of the RNA, and its rates of unfolding and refolding. The effects of proteins that unwind, transcribe, and translate the RNA, as well as drugs that inhibit these processes are determined. 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 human diseases. RNA viruses cause many human diseases including AIDS, flu, hepatitis C, SARS, etc. Malfunctioning RNAs that occur naturally in humans can also cause diseases. Investigation of RNA structure will provide better understanding of RNA function, and can lead to better drugs to cure or prevent human disease.