Howard Hughes Medical Institute, Department of Molecular Biology, and Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, United States.
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, United States.
J Am Chem Soc. 2021 Mar 10;143(9):3267-3279. doi: 10.1021/jacs.0c12955. Epub 2021 Feb 26.
Recent advances in prebiotic chemistry are beginning to outline plausible pathways for the synthesis of the canonical ribonucleotides and their assembly into oligoribonucleotides. However, these reaction pathways suggest that many noncanonical nucleotides are likely to have been generated alongside the standard ribonucleotides. Thus, the oligomerization of prebiotically synthesized nucleotides is likely to have led to a highly heterogeneous collection of oligonucleotides comprised of a wide range of types of nucleotides connected by a variety of backbone linkages. How then did relatively homogeneous RNA emerge from this primordial heterogeneity? Here we focus on nonenzymatic template-directed primer extension as a process that would have strongly enriched for homogeneous RNA over the course of multiple cycles of replication. We review the effects on copying the kinetics of nucleotides with altered nucleobase and sugar moieties, when they are present as activated monomers and when they are incorporated into primer and template oligonucleotides. We also discuss three variations in backbone connectivity, all of which are nonheritable and regenerate native RNA upon being copied. The kinetic superiority of RNA synthesis suggests that nonenzymatic copying served as a chemical selection mechanism that allowed relatively homogeneous RNA to emerge from a complex mixture of prebiotically synthesized nucleotides and oligonucleotides.
近年来，前生物化学领域的进展开始勾勒出合理的途径，用于合成规范的核苷酸，并将其组装成寡核苷酸。然而，这些反应途径表明，许多非规范核苷酸很可能与标准核苷酸一起产生。因此，前生物合成核苷酸的聚合很可能导致了由各种类型的核苷酸通过各种骨架连接组成的高度异质的寡核苷酸混合物。那么，这种原始的异质性是如何产生相对同质的 RNA 呢？在这里，我们关注的是无酶模板指导的引物延伸，这是一个在多个复制循环过程中，强烈富集同质 RNA 的过程。我们回顾了改变碱基和糖部分的核苷酸在作为激活单体存在时以及在掺入引物和模板寡核苷酸时对复制动力学的影响。我们还讨论了三种不同的骨架连接方式，它们都是非遗传性的，并且在被复制时会再生原始 RNA。RNA 合成的动力学优势表明，非酶复制作为一种化学选择机制，使得相对同质的 RNA 能够从复杂的前生物合成核苷酸和寡核苷酸混合物中产生。
