Rolling Circle RNA Synthesis Catalysed by RNA
Rolling Circle RNA Synthesis Catalysed by RNA
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RNA 催化的滚环 RNA 合成
DOI：
10.1101/2021.11.30.470609
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Kristoffersen E
中科院分区：
文献类型：
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作者：
Kristoffersen E
RNA 催化的 RNA 复制被广泛认为是生命第一个遗传系统出现的关键步骤。然而，RNA 复制可能会受到双链 RNA 产物非凡稳定性的阻碍，双链 RNA 产物必须解离才能重新启动下一个复制周期。在这里，我们探索了滚环合成（RCS）作为解决链分离问题的潜在解决方案。我们观察到三联体聚合酶核酶在全长环合成之外通过链置换产生多联体 RNA 产物的持续 RCS。此外，我们还展示了能够自我切割和重新环化的环状锤头核酶的 RCS。因此，类病毒RNA复制途径的所有步骤都可以仅由RNA催化。最后，我们通过分子动力学模拟探索了潜在的 RCS 机制，这表明 RCS 上的构象应变逐渐累积，并且新生链 5' 和 3' 末端不稳定。我们的结果对于 RNA 复制的出现以及理解 RNA 支持复杂遗传过程的潜力具有重要意义。
RNA-catalyzed RNA replication is widely considered a key step in the emergence of life’s first genetic system. However, RNA replication can be impeded by the extraordinary stability of duplex RNA products, which must be dissociated for re-initiation of the next replication cycle. Here, we have explored rolling circle synthesis (RCS) as a potential solution to this strand separation problem. We observe sustained RCS by a triplet polymerase ribozyme beyond full-length circle synthesis with strand displacement yielding concatemeric RNA products. Furthermore, we show RCS of a circular Hammerhead ribozyme capable of self-cleavage and re-circularization. Thus, all steps of a viroid-like RNA replication pathway can be catalyzed by RNA alone. Finally, we explore potential RCS mechanisms by molecular dynamics simulations, which indicate a progressive build-up of conformational strain upon RCS with destabilization of nascent strand 5′-and 3′-ends. Our results have implications for the emergence of RNA replication and for understanding the potential of RNA to support complex genetic processes.