Rout Saroj K, Wunnava Sreekar, Krepl Miroslav, Cassone Giuseppe, Šponer Judit E, Mast Christof B, Powner Matthew W, Braun Dieter
Systems Biophysics and Center for NanoScience, Faculty of Physics, Ludwig-Maximilians-Universität München, Geschwister-Scholl-Platz 1, 80539, Munich, Germany.
Institute of Molecular Physical Science, ETH Zurich, 8093, Zurich, Switzerland.
Nat Commun. 2025 Jun 4;16(1):5193. doi: 10.1038/s41467-025-60359-3.
RNA and proteins are the foundation of life and a natural starting point to explore its origins. However, the prebiotic relationship between the two is asymmetric. While RNA evolved to assemble proteins from amino acids, a significant mirror-symmetric effect of amino acids to trigger the synthesis of RNA was missing. We describe ambient alkaline conditions where amino acids, without additional chemical activators, promote RNA copolymerisation more than 100-fold, starting from prebiotically plausible ribonucleoside-2',3'-cyclic phosphates. The observed effect is explained by acid-base catalysis, with optimal efficiency at pH values near the amine pK. The fold-change in oligomerisation yield is nucleobase-selective, resulting in increased compositional diversity necessary for subsequent molecular evolution and favouring the formation of natural 3'-5' linkages. The elevated pH offers recycling of oligonucleotide sequences back to 2',3'-cyclic phosphates, providing conditions for high-fidelity replication by templated ligation. The findings reveal a clear functional role of amino acids in the evolution of RNA earlier than previously assumed.
RNA和蛋白质是生命的基础,也是探索生命起源的自然起点。然而,两者之间的益生元关系是不对称的。虽然RNA进化为从氨基酸组装蛋白质,但氨基酸触发RNA合成的显著镜像对称效应却不存在。我们描述了一种环境碱性条件,在这种条件下,无需额外的化学激活剂,氨基酸就能促进RNA共聚合超过100倍,起始于益生元上合理的核糖核苷-2',3'-环磷酸酯。观察到的效应是由酸碱催化解释的,在接近胺pK的pH值下效率最佳。寡聚化产率的倍数变化是碱基选择性的,导致后续分子进化所需的组成多样性增加,并有利于天然3'-5'键的形成。升高的pH值使寡核苷酸序列循环回到2',3'-环磷酸酯,为通过模板连接进行高保真复制提供了条件。这些发现揭示了氨基酸在RNA进化中比以前假设的更早的明确功能作用。