Ribosome-Free Translation

在核酸的指导下，多肽的合成是我们所知的生命的关键过程。蛋白质的生物合成是通过翻译进行的。翻译是一个由RNA指导的过程，涉及到一个以RNA为核心的mRNA、tRNAs和核糖体，但很难理解如何从随机序列中产生如此复杂的机制。一定有一种更简单的形式的RNA诱导的多肽合成，然后进化成一个更复杂的系统。一种建议是，这种更简单的形式可能涉及肽RNA，即由核苷酸和氨基酸自发形成的磷酸连接物种。在我们目前的研究中，我们了解到纳米级的RNA结构可以同时有利于多肽RNA和游离肽的形成。此外，我们还建立了第一种无核糖体形式的翻译。根据RNA模板的不同，在没有核糖体或酶的情况下，不同的氨基酸被结合在生长中的多肽RNA的C末端。将这种形式的翻译扩展到更长的序列需要对模板、引物和tRNA物种进行空间控制。为了实现这一点，我们将制备新的氨基酰化接头分子，并使用新的模板结构。我们将测试从核酸纳米技术和非核糖体多肽合成中获得的定位能力所激发的构建。位置控制和动态的、特定于序列的相互作用的结合有望为生命起源和模板指导的编码反应研究中最困难的问题之一提供深入的见解。

The synthesis of peptides, instructed by nucleic acids, is a pivotal process for life as we know it. The biosynthesis of proteins occurs via translation. Translation is an RNA-directed process, involving an mRNA, tRNAs, and ribosomes with an RNA core, but it is difficult to see how so complex a machinery could have emerged from random sequences. There must have been a simpler form of RNA-induced peptide synthesis that then evolved into an ever more sophisticated system. One proposal is that this simpler form may have involved peptido RNA, i.e. phosphoramidate-linked species that form spontaneously from nucleotides and amino acids. In our current study, we learned that nanoscale RNA structures can favor the formation of both peptido RNAs and free peptides. Additionally, we established the first ribosome-free form of translation. Depending on the RNA template, different amino acids are incorporated at the C-terminus of a growing peptido RNA in the absence of ribosomes or enzymes. Extending this form of translation to longer sequences requires spatial control over template, primer and tRNA species. To accomplish this, we will prepare new aminoacylate adaptor molecules and employ new template constructs. We will test constructs inspired by the positioning capabilities known from nucleic acid nanotechnology and from nonribosomal peptide synthesis. The combination of positional control and dynamic, sequence-specific interactions is expected to provide insights into one of the most difficult problems in the study of the origin of life and on template-directed, encoded reaction in general.