MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, United Kingdom.
Department of Molecular Biology and Center for Computational and Integrative Biology, Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, Massachusetts 02114, United States.
J Am Chem Soc. 2022 Aug 3;144(30):13920-13927. doi: 10.1021/jacs.2c05601. Epub 2022 Jul 26.
The first ribozymes are thought to have emerged at a time when RNA replication proceeded via nonenzymatic template copying processes. However, functional RNAs have stable folded structures, and such structures are much more difficult to copy than short unstructured RNAs. How can these conflicting requirements be reconciled? Also, how can the inhibition of ribozyme function by complementary template strands be avoided or minimized? Here, we show that short RNA duplexes with single-stranded overhangs can be converted into RNA stem loops by nonenzymatic cross-strand ligation. We then show that loop-closing ligation reactions enable the assembly of full-length functional ribozymes without any external template. Thus, one can envisage a potential pathway whereby structurally complex functional RNAs could have formed at an early stage of evolution when protocell genomes might have consisted only of collections of short replicating oligonucleotides.
人们认为，第一批核酶出现在 RNA 复制通过非酶模板复制过程进行的时期。然而，功能性 RNA 具有稳定折叠的结构，与短的无结构 RNA 相比，这种结构更难复制。如何调和这些相互冲突的要求？此外，如何避免或最小化互补模板链对核酶功能的抑制？在这里，我们表明，具有单链突出端的短 RNA 双链体可以通过非酶的链间连接转化为 RNA 茎环。然后，我们表明，环封闭连接反应能够在没有任何外部模板的情况下组装全长功能性核酶。因此，可以设想一种潜在的途径，即在早期进化阶段，当原细胞基因组可能仅由短的复制寡核苷酸集合组成时，结构复杂的功能性 RNA 可能已经形成。
