STRUCTURE AND FUNCTION OF NUCLEIC ACIDS

长期目标是能够从其碱基序列推断出RNA分子的三维结构。信使RNA分子转移和解释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制的一部分。RNA加工、信使RNA翻译控制和信使RNA寿命控制中的错误与许多人类疾病有关，包括几种神经退行性疾病，如卢·格里克病。在RNA病毒中，RNA既是遗传信息，也是蛋白质合成的信使。因此，自然产生的RNA和病毒RNA是预防或治愈疾病的药物的突出靶点。到目前为止，绝大多数药物靶标都是蛋白质。了解RNA的三维结构对于理解RNA的功能是至关重要的。RNA分子是由RNA聚合酶根据DNA模板在实验室中合成的，如果需要的话，可以使用13C和15N同位素标记。RNA分子的多维核磁共振光谱提供了质子之间的距离和键周围的扭转角。标准键角和键长，加上核磁共振实验距离和角度，被用于分子动力学模拟，以获得RNA分子中每个原子的坐标。出现在RNA中的代表性结构基序正在确定中。通过测量不同物种的平衡浓度，评估了这些基序(二级和三级结构)相对于单链分子的热力学稳定性。这些信息将导致仅从序列预测RNA结构的改进。RNA结构将有助于理解其功能，并控制RNA在病毒和遗传性疾病中的作用。

The long term goal is to be able to deduce a three-dimensional structure for an RNA molecule from the sequence of its bases. Messenger RNA molecules transfer and interpret the genetic information in DNA to produce proteins. Ribosomal RNAs and transfer RNAs are part 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 diseases 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. Knowledge of the three-dimensional structures of RNAs is crucial to understanding RNA function. The RNA molecules are synthesized in the laboratory by RNA polymerase from a DNA template, using 13C and 15N isotope labeling, if needed. Multidimensional nuclear magnetic resonance spectroscopy of the RNA molecules provides distances between protons, and torsion angles around bonds. Standard bond angles and bond lengths, plus the NMR experimental distances and angles, are used in molecular dynamics simulations to obtain coordinates for each atom in the RNA molecule. Representative structural motifs that occur in RNAs are being determined. The thermodynamic stabilities of these motifs (secondary and tertiary structures) relative to the single-stranded molecules are assessed from measured equilibrium concentrations of the different species. This information will lead to improved prediction of RNA structure from sequence alone. RNA structures will help in understanding function, and in controlling the RNA role in viral and genetic diseases.