Mineral-Promoted RNA Polymerization: Investigating Structural Properties of Catalytic Minerals

拟议工作的目标是通过促进从简单的起始前体分子（单体）形成较长的核糖核酸（RNA）分子（聚合物）来确定可能在早期地球生命起源（OoL）中发挥作用的矿物。在生命和酶之前，有人提出矿物质可能已经充当催化剂，发挥酶的作用，促进聚合。RNA是生物学中最重要的分子之一，因为它能够发挥多种作用。在OoL中，聚合物的形成是重要的，因为低聚物具有呈现不同结构和功能的能力。因此，单体的聚合是从简单的有机前体向最早的类生命细胞发展的关键桥梁步骤。拟议中的工作将有助于国家科学基金会的目标，即促进基础科学在人类提出的最深刻的问题之一，即生命是如何开始开始的进步？拟议的工作还包括许多外联活动，包括在国家公共广播电台编制每周节目和公共科学系列讲座，将科学带给公众，以及鼓励妇女和多样性的外联活动。该基金将资助一名博士后研究人员。因此，拟议的工作也支持国家科学基金会的目标，支持教育和多样性，并培训未来的科学劳动力。矿物，因为他们的反应性和普遍存在，可能有助于生命的起源，从生物地球化学到生物化学的转变。RNA是一种信息载体，有些RNA还可以作为酶，因此RNA被认为是生命起源中DNA和酶的前体。该领域的主要挑战之一是RNA寡聚体的非酶促（益生元）合成，长期以来，矿物质一直被提议作为益生元催化剂。蒙脱石在镁或高浓度碱金属阳离子存在下促进活化的核糖核苷酸聚合的作用已被发现30年，并且一些研究调查了RNA单体在矿物上的吸附，但其他催化矿物尚不清楚。因此，缺乏关于矿物结构和聚合催化效率之间的任何潜在关系的知识。我们建议填补我们知识中的这一空白。对矿物结构、吸附量与催化效率之间的关系提出了三个假设：（1）吸附的核苷酸构象比矿物的吸附量对催化作用更重要;（2）二价或碱金属阳离子应在核苷酸和任何带负电荷的矿物表面之间形成外层三元复合物，因此它们可以容易地被置换，并且核苷酸磷酸仍然可用于磷酸化;和（3）矿物质应该提供纳米限制的环境，其中尽管有大量的水性环境，缩合反应也可以发生。某些矿物，如水钠锰矿、水滑石和沸石被预测具有催化结构。本研究的广泛目标是阐明矿物结构、表面化学、吸附能力、吸附构象和聚合效率之间的任何潜在关系，从而发现新的催化矿物。具体的目的是（1）确定在不存在和存在溶解阳离子的情况下腺苷一磷酸核苷酸的吸附特性;（2）确定各种矿物的核苷酸聚合促进能力;（3）确定促进聚合的矿物上吸附的腺苷一磷酸核苷酸的详细分子水平构象;（4）确定在矿物上吸附的腺苷一磷酸核苷酸的分子水平构象。（4）综合这些结果，建立一个解释蒙脱石催化能力的模型，并对预测的特定矿物的催化活性进行检验。我们将使用紫外-可见分光光度法测定吸附，并通过高效液相色谱法（HPLC）和MALDI-TOF质谱法测定已知催化矿物和新预测矿物上的monoproptides的聚合。吸附单体的构象将通过魔角旋转NMR光谱法和傅立叶变换红外光谱法测定。拟议的工作提供了基于结构的预测催化活性，从而有助于确定新的催化矿物超越蒙脱石。在特定的环境条件下，对更广泛的催化矿物的了解将有助于预测生物分子的生物前聚合反应在其他固体世界上出现生命的可能性，例如，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。

The goal of the proposed work is to identify minerals which could have played a role in the origin of life (OoL) on early Earth by promoting the formation of longer molecules (polymers) of ribonucleic acid (RNA) from simple starting precursor molecules (monomers). Before life and enzymes, it is proposed that minerals may have acted as catalysts to play the role of enzymes in promoting polymerization. RNA is one of the most important molecules in biology because of its ability to play many roles. In the OoL, the formation of polymers is important because oligomers have the ability to take on different structures and functionalities. Thus, polymerization of monomers is a key bridging step in the progress from simple organic precursors towards the earliest life-like cells. The proposed work would contribute to NSF's goal of promoting the progress of fundamental science in one of the most profound questions asked by humankind, which is, how did life begin? The proposed work also includes numerous outreach activities, including the development of a weekly program on National Public Radio as well as a public science lecture series, which would bring science to the general public, and outreach activities to encourage women and diversity. The grant funds would support a post-doctoral researcher. Thus, the proposed work also supports NSF's goal of supporting education and diversity, and training the future scientific workforce.Minerals, because of their reactivity and ubiquity, likely contributed to the origin of life in the transformation from prebiotic geochemistry to biochemistry. RNA is an information- carrier and some RNAs can also act as enzymes, so RNA is believed to have been a precursor to DNA and enzymes in the origins of life. One of the major challenges in the field is the non-enzymatic (prebiotic) synthesis of RNA oligomers, and minerals have long been proposed as prebiotic catalysts. The role of montmorillonite in promoting polymerization of activated ribonucleotides in the presence of magnesium or high concentrations of alkali cations has been known for thirty years, and several studies have investigated RNA monomer adsorption on minerals, but other catalytic minerals are not known. Thus, there is a lack of knowledge about any potential relationships between mineral structure and polymerization catalytic efficiency. We propose to address this gap in our knowledge. We propose three hypotheses for the relationship between the mineral structure, its adsorption capacity and its catalytic efficiency: (1) adsorbed ribonucleotide conformation is more important than adsorption capacity of the mineral for catalysis; (2) the divalent or alkali cations should form outer-sphere ternary complexes between the nucleotide and any negatively charged mineral surface, so that they can be easily displaced and the nucleotide phosphate is still available for phosphorylation; and (3) the mineral should provide a nanoconfined environment where the condensation reaction can occur despite bulk aqueous environment. Specific minerals, such as birnessite, hydrotalcite and zeolites are predicted to have catalytic structures. The broad goals of the present study are to shed light on any potential relationships between mineral structure, surface chemistry, adsorption capacity, adsorbed conformation and polymerization efficiency, thus, discovering new catalytic minerals. The specific aims are (1) to determine the adsorption characteristics of adenosine monophosphate nucleotides in the absence and presence of dissolved cations;(2) to determine the nucleotide polymerization-promoting ability of various minerals; (3) to determine the detailed molecular-level conformation of adsorbed mononucleotides on minerals that promote polymerization; and (4) to synthesize these results to develop a model for explaining the catalytic ability of montmorillonite and to test the predicted catalytic activity of specific minerals. We will determine adsorption using UV-Vis spectrophotometry, and polymerization of mononucleotides on the known catalytic mineral and on the newly predicted minerals by High Performance Liquid Chromatography (HPLC) and MALDI-TOF Mass Spectrometry. Conformation of adsorbed monomer will be determined by Magic Angle Spinning NMR spectroscopy and by Fourier Transform Infra-Red Spectroscopy. The proposed work provides structure-based predictions for catalytic activity, thus helping to identify new catalytic minerals beyond montmorillonite. Knowledge of a wider variety of catalytic minerals under specific environmental conditions will help predict the plausibility of prebiotic polymerization reactions of biomolecules for life's emergence on other solid worlds, e.g., Mars.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.