EAGER: Exploring the RNA World and the RNA-peptide world hypothesis using a novel Dynamic Combinatorial Chemistry (DCC) system

EAGER：使用新型动态组合化学 (DCC) 系统探索 RNA 世界和 RNA 肽世界假说

• 批准号: 2227347
• 负责人: Madhan Tirumalai
• 金额: $ 30万
• 依托单位: University of Houston
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2227347&HistoricalAwards=false
• 关键词: EAGER; Exploring; RNA; World; peptide

The universal biomolecule RNA possesses dual abilities to serve as a repository for genetic information and to catalyze reactions. These properties make RNA unique and different from the other two biomolecules, DNA and proteins, which led to the idea that an early ‘RNA World’ may have existed. An alternate hypothesis is rapidly gaining traction – that RNA and peptides both contributed to early molecular evolution by mutually supporting each other. Understanding the potential events that might have occurred in an ‘RNA World’, or ‘RNA-Peptide’ world, is important to understand the origins and early history of life. A novel Dynamic Combinatorial Chemistry (DCC) system will be employed to address how RNAs recombine when subjected to cycles of cleavage and ligation under laboratory conditions. The work will be carried out at the University of Houston, a minority serving institution. Undergraduate students will be trained during the course of the project and have the opportunity to co-author publications. Additionally, the project will support public education and outreach on topics related to the origin and early history of living systems.In the DCC system, one enzyme (benzonase) cleaves RNAs, resulting in products with a 3’ hydroxyl and 5’ phosphate, which are then ligated by another enzyme (T4 RNA ligase). This system will be employed to evaluate the competing RNA world and RNA-peptide world theories. If a dynamically changing population of small RNAs continues to change independently in the absence of amino acids/peptides, it would support existence of an extended RNA World. If instead, the presence of peptides and/or amino acids significantly impacts the RNA sequence diversity, it would suggest a rapid transition to an RNA-Peptide World could have occurred. The findings will advance understanding of the role of RNA (and peptides/amino acids) in the origins of life besides providing a novel and unique approach to exploring RNA sequence space. For example, such a system applied to sequences from RNA viruses could shed light on the dynamics of RNA genome recombination.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

通用生物分子RNA具有双重能力，作为遗传信息的储存库和催化反应。这些特性使RNA与其他两种生物分子DNA和蛋白质不同，这导致了早期“RNA世界”可能存在的想法。另一种假说正在迅速获得支持-RNA和肽都通过相互支持而促进了早期分子进化。了解“RNA世界”或“RNA肽”世界中可能发生的潜在事件，对于了解生命的起源和早期历史非常重要。一种新的动态组合化学（DCC）系统将被用来解决如何RNA重组时，在实验室条件下进行切割和连接循环。这项工作将在休斯顿大学进行，这是一个少数民族服务机构。本科生将在项目过程中接受培训，并有机会共同撰写出版物。此外，该项目还将支持有关生命系统起源和早期历史的公共教育和宣传。在DCC系统中，一种酶（benzonase）切割RNA，产生具有3'羟基和5'磷酸的产物，然后由另一种酶（T4 RNA连接酶）连接。这个系统将被用来评估竞争的RNA世界和RNA-肽世界理论。如果一个动态变化的小RNA群体在没有氨基酸/肽的情况下继续独立变化，那么它将支持扩展的RNA世界的存在。相反，如果肽和/或氨基酸的存在显着影响RNA序列的多样性，这将表明可能发生了向RNA-肽世界的快速转变。这些发现将促进对RNA（和肽/氨基酸）在生命起源中的作用的理解，同时为探索RNA序列空间提供了一种新颖而独特的方法。例如，应用于RNA病毒序列的这种系统可以揭示RNA基因组重组的动力学。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。