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STRUCTURE AND FUNCTION OF NUCLEIC ACIDS

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
依托单位国家:
美国
项目类别:
财政年份:
1976
资助国家:
美国
项目状态:
已结题
起止时间:
1976-12-01 至 1994-11-30

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项目成果

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中文摘要
翻译
长期目标是能够利用DNA或RNA的序列, 预测其天然细胞或 细胞外环境 由于结构意味着功能,因此可以 了解并学会控制它的生物功能。 的合成 每一种蛋白质都是由信使RNA指定的。 信使RNA是 通过处理从DNA转录的初级转录物而产生。 的 这些核酸的特定折叠构象对于 正确的功能。 RNA病毒和DNA病毒的复制 需要合成RNA分子。 因此,序列的知识和 致病性病毒RNA的折叠可以揭示预防病毒感染的方法, 复制以及治愈或预防病毒性疾病。 遗传疾病 和常染色体遗传疾病,如癌症,是由改变, DNA序列。 了解序列的变化如何 发生,以及这些变化对复制和 DNA的转录,以及RNA的加工和翻译。 核酸序列与构象的关系及其作用 蛋白质测序是许多人类健康问题的核心。 寡核苷酸将被合成,其可以形成重要的结构 RNA和DNA中存在的基序。 它们的序列和环境 以确定什么样的结构形成和什么样的条件下, 为它们的形成所需。 寡核苷酸与以下物质的反应性 酶和化学试剂将揭示双链和单链 链区域。 光谱测量,构象。 热力学 表征不同基序的稳定性的参数将 不同构象之间的交换将通过NMR或通过NMR来确定。 温度跳跃法 在RNA中要研究的结构元件包括假结、发夹、 环、碱基错配、内环、凸起和左手Z-RNA。 在DNA中,基序包括碱基-碱基错配、端粒序列和 包括鸟嘌呤碱基对的双链、三链和四链复合物。
英文摘要
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.
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