Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152, Martinsried, Germany.
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
Angew Chem Int Ed Engl. 2021 Feb 8;60(6):2952-2957. doi: 10.1002/anie.202010918. Epub 2020 Dec 10.
RNA-catalyzed RNA ligation is widely believed to be a key reaction for primordial biology. However, since typical chemical routes towards activating RNA substrates are incompatible with ribozyme catalysis, it remains unclear how prebiotic systems generated and sustained pools of activated building blocks needed to form increasingly larger and complex RNA. Herein, we demonstrate in situ activation of RNA substrates under reaction conditions amenable to catalysis by the hairpin ribozyme. We found that diamidophosphate (DAP) and imidazole drive the formation of 2',3'-cyclic phosphate RNA mono- and oligonucleotides from monophosphorylated precursors in frozen water-ice. This long-lived activation enables iterative enzymatic assembly of long RNAs. Our results provide a plausible scenario for the generation of higher-energy substrates required to fuel ribozyme-catalyzed RNA synthesis in the absence of a highly evolved metabolism.
RNA 催化的 RNA 连接被广泛认为是原始生物学的关键反应。然而，由于典型的化学途径与核酶催化不兼容，因此尚不清楚前生物系统如何产生和维持激活的构建块池，这些构建块对于形成越来越大和复杂的 RNA 是必需的。在此，我们证明了在适用于发夹核酶催化的反应条件下，RNA 底物的原位激活。我们发现二氨基磷酸（DAP）和咪唑在冷冻水冰中从单磷酸前体中驱动 2'，3'-环磷酸 RNA 单核苷酸和寡核苷酸的形成。这种长寿命的激活使长 RNA 的酶促组装得以迭代进行。我们的结果为在没有高度进化的代谢的情况下，为驱动核酶催化的 RNA 合成所需的高能底物的产生提供了一个合理的方案。
