Sprecher
Beschreibung
The replication of genetic information is closely linked to the origin of life. The molecular basis of replication is genetic copying, a reaction in which the sequence of a template strand is transmitted to a copy. In cells, genetic copying is catalyzed by polymerases, which, in turn, are encoded in genes, making the origin of replication a difficult evolutionary problem. One proposal how this problem may have been solved posits that RNA was the biocatalyst for its own replication. This proposal is part of the 'RNA world' hypothesis [1]. Again, there is a dilemma, as the known RNA-based polymerases [2] are too large to have a reasonable probability of being formed spontaneously from nucleotides oligomerizing into random sequences. A simpler scenario relies on base pairing and chemical reactivity alone. In this scenario, nucleotides oligomerize to oligonucleotides, and template-directed chain extension reactions account for the transmission of genetic information. Experimental studies on enzyme-free genetic copying were pioneered by the Orgel group [3], and have been performed extensively by Szostak [4] and others. We have studied the factors limiting the yield of copying with activated ribonucleotides [5], and we then established in situ activation combined with organocatalysis to reduce inhibition [6]. Recently, we reported dinucleotides as building blocks for copying [7]. Building on this work and the results from the first enzyme-free replication of DNA sequences [8], we have now identified reaction conditions that lead to the copying of up to 12 nucleotides in an RNA template strand [9].
References
1. W. Gilbert, The RNA world. Nature 1986, 319, 618.
2. J. Attwater, A. Raguram, A.S. Morgunov, E. Gianni, P. Holliger, eLife 2018, 7, e35255.
3. I. A. Kozlov, L. E. Orgel, Mol. Biol. 2000, 34, 781-789.
4. T. Walton, W. Zhang, L. Li, C.P. Tam, J.W. Szostak, Angew. Chem. Int. Ed. 2019, 58, 10812-10819.
5. C. Deck, M. Jauker, C. Richert, Nat. Chem. 2011, 3, 603-608.
6. M. Jauker, H. Griesser, C. Richert, Angew. Chem. Int. Ed. 2015, 54, 14559-14563.
7. M. Sosson, D. Pfeffer, C. Richert, Nucleic Acids Res. 2019, 47, 3836-3845.
8. E. Hänle, C. Richert, Angew. Chem. Int. Ed. 2018, 57, 8911-8915.
9. G. Leveau, D. Pfeffer, B. Altaner, E. Kervio, F. Welsch, U. Gerland, C. Richert, Angew. Chem. Int. Ed. 2022, 61, e202203067.
