Arriola Joshua T, Poordian Shayan, Valdivia Estefanía Martínez, Le Tommy, Leman Luke J, Schellinger Joan G, Müller Ulrich F
Department of Chemistry & Biochemistry, University of California, San Diego La Jolla CA 92093 USA
Department of Chemistry & Biochemistry, University of San Diego San Diego CA 92110 USA.
RSC Chem Biol. 2024 Sep 12;5(11):1122-31. doi: 10.1039/d4cb00129j.
Catalytic RNAs (ribozymes) were central to early stages of life on earth. The first ribozymes probably emerged in the presence of prebiotically generated peptides because amino acids can be generated under abiotic conditions, and amino acids can oligomerize into peptides under prebiotically plausible conditions. Here we tested whether the presence of prebiotically plausible peptides could have aided the emergence of ribozymes, by an selection of self-triphosphorylation ribozymes from random sequence in the presence of ten different octapeptides. These peptides were composed of ten different, prebiotically plausible amino acids, each as mixture of d- and l-stereoisomers. After five rounds of selection and high throughput sequencing analysis, ten ribozymes that appeared most promising for peptide benefits were tested biochemically for possible benefits from each of the ten peptides. The strongest peptide benefit enhanced ribozyme activity by 2.6-fold, similar to the effect from an increase in the pH by one-half unit. Four arbitrarily chosen ribozymes from a previous selection without peptides showed no significant change in their activity in the presence of the ten peptides. Therefore, the used prebiotically plausible peptides - peptides without evolutionarily optimized sequence, without cationic or aromatic side chains - did not provide a strong benefit for the emergence of ribozyme activity. This finding stands in contrast to previously identified polycationic peptides, conjugates between peptides and polyaromatic hydrocarbons, and modern mRNA encoded proteins, all of which can strongly increase ribozyme function. The results are discussed in the context of origins of life.
催化性RNA（核酶）在地球生命的早期阶段起着核心作用。第一批核酶可能是在益生元生成的肽存在的情况下出现的，因为氨基酸可以在非生物条件下生成，并且氨基酸可以在益生元合理的条件下寡聚成肽。在这里，我们通过在十种不同的八肽存在的情况下从随机序列中选择自我三磷酸化核酶，测试了益生元合理的肽的存在是否有助于核酶的出现。这些肽由十种不同的、益生元合理的氨基酸组成，每种氨基酸都是d-和l-立体异构体的混合物。经过五轮筛选和高通量测序分析后，对十种最有希望从肽中获益的核酶进行了生化测试，以检测这十种肽中每种肽可能带来的益处。最强的肽益处使核酶活性提高了2.6倍，类似于pH值升高0.5个单位的效果。从之前没有肽的筛选中任意选择的四种核酶在这十种肽存在的情况下其活性没有显著变化。因此，所使用的益生元合理的肽——没有经过进化优化序列、没有阳离子或芳香侧链的肽——并没有为核酶活性的出现提供强大的益处。这一发现与之前鉴定的聚阳离子肽、肽与多环芳烃的缀合物以及现代mRNA编码的蛋白质形成对比，所有这些都能强烈增强核酶功能。我们在生命起源的背景下讨论了这些结果。
