Prywes Noam, Blain J Craig, Del Frate Francesca, Szostak Jack W
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, United States.
Department of Molecular Biology and Center for Computational and Integrative Biology, Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, United States.
Elife. 2016 Jun 28;5:e17756. doi: 10.7554/eLife.17756.
The nonenzymatic replication of RNA is a potential transitional stage between the prebiotic chemistry of nucleotide synthesis and the canonical RNA world in which RNA enzymes (ribozymes) catalyze replication of the RNA genomes of primordial cells. However, the plausibility of nonenzymatic RNA replication is undercut by the lack of a protocell-compatible chemical system capable of copying RNA templates containing all four nucleotides. We show that short 5'-activated oligonucleotides act as catalysts that accelerate primer extension, and allow for the one-pot copying of mixed sequence RNA templates. The fidelity of the primer extension products resulting from the sequential addition of activated monomers, when catalyzed by activated oligomers, is sufficient to sustain a genome long enough to encode active ribozymes. Finally, by immobilizing the primer and template on a bead and adding individual monomers in sequence, we synthesize a significant part of an active hammerhead ribozyme, forging a link between nonenzymatic polymerization and the RNA world.
RNA的非酶促复制是核苷酸合成的前生物化学与规范的RNA世界之间的一个潜在过渡阶段，在RNA世界中，RNA酶（核酶）催化原始细胞RNA基因组的复制。然而，由于缺乏一种能够复制包含所有四种核苷酸的RNA模板的原生细胞兼容化学系统，非酶促RNA复制的合理性受到了削弱。我们表明，短的5'-活化寡核苷酸作为催化剂可加速引物延伸，并允许一锅法复制混合序列RNA模板。当由活化寡聚物催化时，通过顺序添加活化单体产生的引物延伸产物的保真度足以维持一个足够长的基因组以编码活性核酶。最后，通过将引物和模板固定在珠子上并按顺序添加单个单体，我们合成了活性锤头状核酶的很大一部分，在非酶促聚合与RNA世界之间建立了联系。
