MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
Institut für Pharmazie und Molekulare Biotechnologie, Universität Heidelberg, Heidelberg 69120, Germany.
J Am Chem Soc. 2023 Jul 26;145(29):15971-15980. doi: 10.1021/jacs.3c03931. Epub 2023 Jul 12.
The encoding step of translation involves attachment of amino acids to cognate tRNAs by aminoacyl-tRNA synthetases, themselves the product of coded peptide synthesis. So, the question arises─before these enzymes evolved, how were primordial tRNAs selectively aminoacylated? Here, we demonstrate enzyme-free, sequence-dependent, chemoselective aminoacylation of RNA. We investigated two potentially prebiotic routes to aminoacyl-tRNA acceptor stem-overhang mimics and analyzed those oligonucleotides undergoing the most efficient aminoacylation. Overhang sequences do not significantly influence the chemoselectivity of aminoacylation by either route. For aminoacyl-transfer from a mixed anhydride donor strand, the chemoselectivity and stereoselectivity of aminoacylation depend on the terminal three base pairs of the stem. The results support early suggestions of a second genetic code in the acceptor stem.
翻译的编码步骤涉及到氨酰-tRNA 合成酶将氨基酸连接到相应的 tRNA 上，而氨酰-tRNA 合成酶本身就是编码肽合成的产物。因此，问题出现了——在这些酶进化之前，原始的 tRNA 是如何被选择性氨酰化的？在这里，我们展示了无酶、序列依赖性、化学选择性的 RNA 氨酰化。我们研究了两种潜在的前生物途径来模拟氨酰-tRNA 受体茎-悬垂，并分析了那些经历最有效氨酰化的寡核苷酸。悬垂序列对两种途径的氨酰化的化学选择性都没有显著影响。对于混合酸酐供体链上的氨酰转移，氨酰化的化学选择性和立体选择性取决于茎的末端三个碱基对。结果支持了在受体茎中存在第二个遗传密码的早期建议。
