The prebiotic origin of the RNA nucleosides

Professor Dr. Thomas Carell, Center for Integrative Protein Science at the Department of Chemistry, Ludwig Maximilians University, Munich

Abstract: The widely accepted RNA world hypothesis suggests that life first emerged from RNA, which is able to (self)-replicate and evolve. Replication of RNA requires formation of the complementary pyrimidine-purine Watson-Crick base pairs A:U and G:C, which are a prerequisite for accurate genetic information transfer. Although prebiotic pathways to RNA building blocks have been reported, no pathway has been able to generate all four constituents of RNA simultaneously.^{[1, 2]} We recently discovered a new pathway (FaPy-pathway) that is able to generate purine nucleosides under plausible prebiotic conditions.^[3] The formation of the purine RNA building blocks is driven exclusively by fluctuations of physicochemical parameters such as pH, temperature and concentration. These conditions allowed in addition the parallel formation of a variety of non-canonical purine nucleosides as living molecular fossil of an early abiotic world.^[4] Many of the formed non-canonical RNA building blocks are today assumed to have been part of the genetic system of the last universal common ancestor (LUCA).^[5] We therefore suggest that these non-canonical nucleosides were formed in the abiotic phase of the origin of life. In order to find a prebiotically plausible scenario for the parallel formation of purine and pyrimidine bases to create the fundamental Watson-Crick base pairing system, we developed new prebiotically plausible chemistry to pyrimidines that are compatible with our purine procedures. This was meant to provide all four RNA building blocks in the same geochemical environment.^[6] We found that the reaction of cyanoacetylene with hydroxylamine is a perfect starting point. It creates first amino-isoxazoles in high yields from which the pyrimidines are easily formed. The new chemistry also affords the naturally occurring 5’-mono- and 5’-di-phosphorylated ribosides exclusively as their furanosides. This observation now provides a plausible explanation for why these thermodynamically disfavoured furanosidic constitutional isomers are exclusively present in the backbone of RNA and DNA. Our results show that all central constituents of RNA could have been part of the same prebiotic nucleoside/tide pool, as a prerequisite for RNA to evolve on early Earth.^[6]

Our chemistry suggest that the formation of RNA on the early earth was not guided by chance but an inevitable consequence of early earth chemistry.

Literature:

[1] Powner et al., Nature 459, 239 (2009)
[2] Kim, H.-J.; Benner, S.; PNAS 114, 11315 (2017)
[3] Becker et al., Science 352, 833 (2016)
[4] Becker et al., Nat. Commun. 9, 163 (2018)
[5] Weiss et al., Nat. Microbiol. 1, 16116 (2016)
[6] Becker et al. Science 366, 86-78 (2019.

Host: Prof. Kurt V. Gothelf, iNANo & Dept. of Chemistry