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

通用生物分子RNA具有作为遗传信息储存库和催化反应的双重能力。这些特性使RNA与众不同，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关注——RNA和多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）系统将被用于解决rna在实验室条件下受到切割和连接循环时如何重组。这项工作将在休斯顿大学进行，这是一所少数族裔服务机构。本科生将在项目过程中接受培训，并有机会共同发表论文。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（苯并酶）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。该系统将用于评价竞争性的RNA世界和RNA-肽世界理论。如果一个动态变化的小RNA群体在缺乏氨基酸/肽的情况下继续独立变化，它将支持一个扩展的RNA世界的存在。相反，如果肽和/或氨基酸的存在显著影响RNA序列多样性，则表明可能已经发生了向RNA-肽世界的快速过渡。这些发现将促进对RNA（以及肽/氨基酸）在生命起源中的作用的理解，并为探索RNA序列空间提供一种新颖而独特的方法。例如，将这种系统应用于RNA病毒序列可以揭示RNA基因组重组的动力学。该奖项反映了美国国家科学基金会的法定使命，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。

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.