STRUCTURE AND FUNCTION OF NUCLEIC ACIDS

长期目标是能够从RNA分子的碱基序列推断出其三维结构。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器的一部分。 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Lou Gehrig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，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标。 到目前为止，绝大多数药物靶点都是蛋白质。了解RNA的三维结构对于理解RNA的功能至关重要。 RNA分子在实验室中通过RNA聚合酶从DNA模板合成，如果需要，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NMR实验距离和角度，用于分子动力学模拟，以获得RNA分子中每个原子的坐标。 RNA中出现的代表性结构基序正在确定中。 这些图案（二级和三级结构）相对于单链分子的热力学稳定性进行评估，从不同物种的平衡浓度测量。 这一信息将导致改进的预测RNA结构从序列单独。RNA结构将有助于理解RNA的功能，并控制RNA在病毒和遗传疾病中的作用。

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.