PDF(Pubmed)
Abstract：
The emergence of RNA on the early Earth is likely to have been influenced by chemical and physical processes that acted to filter out various alternative nucleic acids. For example, UV photostability is thought to have favored the survival of the canonical nucleotides. In a recent proposal for the prebiotic synthesis of the building blocks of RNA, ribonucleotides share a common pathway with arabino- and threo-nucleotides. We have therefore investigated non-templated primer extension with 2-aminoimidazole-activated forms of these alternative nucleotides to see if the synthesis of the first oligonucleotides might have been biased in favor of RNA. We show that non-templated primer extension occurs predominantly through 5\'-5\' imidazolium-bridged dinucleotides, echoing the mechanism of template-directed primer extension. Ribo- and arabino-nucleotides exhibited comparable rates and yields of non-templated primer extension, whereas threo-nucleotides showed lower reactivity. Competition experiments confirmed the bias against the incorporation of threo-nucleotides. The incorporation of an arabino-nucleotide at the end of the primer acts as a chain terminator and blocks subsequent extension. These biases, coupled with potentially selective prebiotic synthesis, and the templated copying that is known to favour the incorporation of ribonucleotides, provide a plausible model for the effective exclusion of arabino- and threo-nucleotides from primordial oligonucleotides.
摘要：
早期地球上RNA的出现可能受到化学和物理过程的影响，这些过程可以过滤掉各种替代核酸。例如,UV光稳定性被认为有利于规范核苷酸的存活。在最近关于RNA结构单元的益生元合成的提议中，核糖核苷酸与阿拉伯和苏核苷酸共享一个共同的途径。因此,我们已经研究了具有这些替代核苷酸的2-氨基咪唑激活形式的非模板化引物延伸,以观察第一寡核苷酸的合成是否可能偏向于RNA。我们表明，非模板化引物延伸主要通过5'-5'咪唑鎓桥接二核苷酸发生，呼应模板导向引物延伸的机制。核糖-和阿拉伯-核苷酸表现出相当的速率和产量的非模板引物延伸，而threo-核苷酸显示较低的反应性。竞争实验证实了对三核苷酸掺入的偏见。在引物末端掺入阿拉伯糖核苷酸充当链终止子并阻断随后的延伸。这些偏见，加上潜在的选择性益生元合成，以及已知有利于核糖核苷酸掺入的模板复制，为从原始寡核苷酸中有效排除阿拉伯和苏核苷酸提供了一个合理的模型。
