Functional RNAs exhibit tolerance for non-heritable 2′-5′ versus 3′-5′ backbone heterogeneity

Functional RNAs exhibit tolerance for non-heritable 2′-5′ versus 3′-5′ backbone heterogeneity
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DOI:
10.1038/nchem.1623
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发表时间:
2013-05-01
期刊:
影响因子:
21.8
通讯作者:
Szostak, Jack W.
Szostak, Jack W.
中科院分区:
化学1区
文献类型:
--
作者:
Engelhart, Aaron E.;Powner, Matthew W.;Szostak, Jack W.

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一个合理的非酶RNA复制过程将大大简化从生命前化学到简单生物学的过渡模型。然而,所有已知的用于RNA模板的化学复制的条件导致合成含有2 '-5'和3 '-5'键的混合物的互补链,而不是如在当代RNA中发现的仅3 '-5'键的选择性合成。在这里,我们表明,这样的骨干异质性是兼容的RNA折叠成定义的三维结构,保留分子识别和催化性能,因此,不会阻止功能性RNA,如核酶的进化。此外,相同的骨架异质性降低了RNA双链体的解链温度,否则RNA双链体对于热链分离来说太稳定。通过允许复制链解离,这种异质性可能是允许RNA作为第一种生物聚合物出现的基本特征之一。
A plausible process for non-enzymatic RNA replication would greatly simplify models of the transition from prebiotic chemistry to simple biology. However, all known conditions for the chemical copying of an RNA template result in the synthesis of a complementary strand that contains a mixture of 2'-5' and 3'-5' linkages, rather than the selective synthesis of only 3'-5' linkages as found in contemporary RNA. Here we show that such backbone heterogeneity is compatible with RNA folding into defined three-dimensional structures that retain molecular recognition and catalytic properties and, therefore, would not prevent the evolution of functional RNAs such as ribozymes. Moreover, the same backbone heterogeneity lowers the melting temperature of RNA duplexes that would otherwise be too stable for thermal strand separation. By allowing copied strands to dissociate, this heterogeneity may have been one of the essential features that allowed RNA to emerge as the first biopolymer.