STRUCTURE AND FUNCTION OF NUCLEIC ACIDS

核酸的结构和功能

• 批准号: 2168521
• 负责人: IGNACIO TINOCO
• 金额: $ 37.47万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 1976
• 资助国家: 美国
• 起止时间: 1976-12-01 至 1994-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2168521
• 关键词: chemical structure function; chromatography; circular dichroism; conformation; gel electrophoresis; guanine nucleoside; messenger RNA; nuclear magnetic resonance spectroscopy; nucleic acid chemical synthesis; nucleic acid hybridization; nucleic acid sequence; nucleic acid structure; nucleobase; oligonucleotides; temperature jump; thermodynamics

The long-term goal is to be able to use the sequence of a DNA or RNA to predict its three dimensional structure in its natural cellular or extracellular environment. As structure implies function, one can then understand and learn to control its biological function. The synthesis of every protein is specified by a messenger RNA. The messenger RNA is produced by processing a primary transcript transcribed from DNA. The specific folded conformations of these nucleic acids are essential for their correct function. Replication of RNA viruses and DNA viruses requires synthesis of RNA molecules. Thus, knowledge of the sequence and folding of a pathogenic viral RNA can reveal methods for preventing viral replication, and curing or preventing the viral disease. Genetic diseases and autosomal genetic diseases, such as cancer, are caused by a change in sequence of DNA. It is vital to understand how the changes in sequence can occur, and what the effects of these changes are on the replication and transcription of the DNA, and on the processing and translation of the RNA. The relation between nucleic acid sequence and conformation, and its role in protein sequence is central to many problems of human health. Oligonucleotides will be synthesized that can form important structural motifs present in RNA and DNA. Their sequences and their environments will be varied to determine what structures do form and what conditions are required for their formation. Reactivity of the oligonucleotides to enzymes and to chemical reagents will reveal double strand and single strand regions. Spectroscopic measurements, conformations. Thermodynamic parameters which characterize the stabilities of the different motifs will exchange between different conformations will be determined by NMR, or by temperature-jump methods. The structural elements to be studied in RNA include pseudoknots, hairpin loops, base-base mismatches, internal loops, bulges, and left-handed Z-RNA. In DNA the motifs include base-base mismatches, telomeric sequences, and two-, three- and four-stranded complexes involving guanine base pairs.

长期目标是能够使用DNA或RNA的序列 预测其自然细胞或 细胞外环境。 由于结构暗示功能，然后可以 了解并学会控制其生物学功能。 合成 每种蛋白质都是由信使RNA指定的。 Messenger RNA是 通过处理从DNA转录的主要转录本产生。 这 这些核酸的特定折叠构象对于 它们的正确功能。 RNA病毒和DNA病毒的复制 需要合成RNA分子。 因此，了解顺序和 致病性病毒RNA的折叠可以揭示预防病毒的方法 复制，治愈或预防病毒疾病。 遗传疾病 常染色体遗传疾病（例如癌症）是由变化引起的 DNA的序列。 了解序列的变化如何可以 发生，以及这些变化的影响对复制和 DNA的转录以及RNA的加工和翻译。 核酸序列与构象之间的关系及其作用 在蛋白质中，序列是许多人类健康问题的核心。 将合成寡核苷酸，以形成重要的结构 RNA和DNA中存在的图案。 他们的序列和环境将 变化以确定哪些结构的形式以及哪些条件是 他们的形成所必需的。 寡核苷酸的反应性 酶和化学试剂将揭示双链和单一酶 链区域。 光谱测量，构象。 热力学 表征不同主题稳定性的参数将 不同构象之间的交换将由NMR或 温度跳跃方法。 在RNA中要研究的结构元素包括假诺，发夹 循环，基碱不匹配，内部环，凸起和左手Z-RNA。 在DNA中，基序包括基本基匹配，端粒序列和 涉及鸟嘌呤碱基对的两，三，四链的复合物。