Non-Enzymatic RNA Replication

非酶促 RNA 复制

• 批准号: 1607034
• 负责人: Jack Szostak
• 金额: $ 100万
• 依托单位: Massachusetts General Hospital
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1607034&HistoricalAwards=false
• 关键词: Non; Enzymatic; RNA; Replication

This project is jointly funded by the Chemistry of Life Processes Program in the Division of Chemistry, and the Genetic Mechanisms and Systems and Synthetic Biology Clusters in the Division of Molecular and Cellular Biosciences.Life is thought to have emerged on the early earth as a consequence of the chemistry of the young planet. Subsequently, there was assembly into simple cells that could grow, divide and evolve. Such cells were probably composed of a cell membrane that enclosed a primitive version of RNA that could store useful information and also carry out simple cellular functions. At present, there is a lack of a full understanding of how genetic materials such as RNA could have been copied before the evolution of enzymes. This project involves a series of experiments aimed at achieving fast and accurate non-enzymatic copying of short RNA strands. The ability to copy RNA in a purely chemical manner is an essential step towards the goal of assembling simple living cells from inanimate chemicals. This in turn would contribute greatly to our understanding of the origin of life on the early earth, and to assessing the likelihood that life might exist on other planets. Since the Origin of Life and the search for life in the Universe are topics of great public interest, this work contributes to public engagement with science as well as to the training of many young scientists.This project involves experimental studies aimed at attaining a better understanding of the chemical reaction mechanisms involved in non-enzymatic template-directed RNA replication. The methodology involves modern structural methods such as X-ray crystallography and NMR spectroscopy, together with reaction kinetics and molecular modeling. In addition, modified nucleotides that may have been present on the early earth and that may lead to faster and more accurate copying of RNA templates are being synthesized and characterized. The project also includes investigations of high energy chemical compounds that could have supplied the energy needed to drive RNA replication. The ability to chemically replicate RNA molecules that are long enough to encode ribozyme catalysts would help in understanding how very simple living cells could be reconstituted from individual chemical components.

该项目由化学系的生命过程化学项目以及分子和细胞生物科学系的遗传机制和系统以及合成生物学集群联合资助。生命被认为是由于年轻行星的化学作用而在早期地球上出现的。随后，组装成可以生长、分裂和进化的简单细胞。 这些细胞可能由细胞膜组成，细胞膜内含原始的RNA，可以存储有用的信息并执行简单的细胞功能。 目前，人们对 RNA 等遗传物质在酶进化之前是如何复制的还缺乏充分的了解。该项目涉及一系列实验，旨在实现短 RNA 链的快速、准确的非酶复制。以纯化学方式复制 RNA 的能力是实现从无生命化学物质组装简单活细胞这一目标的重要一步。这反过来将极大地有助于我们了解早期地球上生命的起源，并评估其他行星上可能存在生命的可能性。由于生命起源和在宇宙中寻找生命是公众极大兴趣的话题，这项工作有助于公众参与科学以及培训许多年轻科学家。该项目涉及实验研究，旨在更好地理解非酶模板指导的 RNA 复制所涉及的化学反应机制。该方法涉及 X 射线晶体学和核磁共振波谱等现代结构方法，以及反应动力学和分子建模。此外，早期地球上可能存在的修饰核苷酸正在被合成和表征，这些修饰核苷酸可能会导致更快、更准确的 RNA 模板复制。 该项目还包括对高能化合物的研究，这些化合物可以提供驱动 RNA 复制所需的能量。化学复制足够长以编码核酶催化剂的RNA分子的能力将有助于理解如何从单个化学成分重建非常简单的活细胞。