Ice as a protocellular medium for RNA replication

Attwater, James; Wochner, Aniela; Pinheiro, Vitor B.; Coulson, Alan; Holliger, Philipp

doi:10.1038/ncomms1076

Cited by 144 publications

(164 citation statements)

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“…Interestingly, the plausibility of ice as a matrix has also been discussed with respect to other aspects about the origin of metabolism. Ice may have helped to establish compartmentalization, essential for any form of metabolism, and it enables the synthesis of nucleobases (29)(30)(31)(32) and supports a nonenzymatic polymerization and a template-directed mechanism for copying RNA (33)(34)(35). Freeze-thaw cycles thus could have helped to achieve both the copying of nucleic acids and nonenzymatic reactions that form the metabolic components of RNA and DNA.…”

Section: Discussionmentioning

confidence: 99%

Nonenzymatic gluconeogenesis-like formation of fructose 1,6-bisphosphate in ice

Messner

Driscoll

Piedrafita

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The evolutionary origins of metabolism, in particular the emergence of the sugar phosphates that constitute glycolysis, the pentose phosphate pathway, and the RNA and DNA backbone, are largely unknown. In cells, a major source of glucose and the large sugar phosphates is gluconeogenesis. This ancient anabolic pathway (re-)builds carbon bonds as cleaved in glycolysis in an aldol condensation of the unstable catabolites glyceraldehyde 3-phosphate and dihydroxyacetone phosphate, forming the much more stable fructose 1,6-bisphosphate. We here report the discovery of a nonenzymatic counterpart to this reaction. The in-ice nonenzymatic aldol addition leads to the continuous accumulation of fructose 1,6-bisphosphate in a permanently frozen solution as followed over months. Moreover, the in-ice reaction is accelerated by simple amino acids, in particular glycine and lysine. Revealing that gluconeogenesis may be of nonenzymatic origin, our results shed light on how glucose anabolism could have emerged in early life forms. Furthermore, the amino acid acceleration of a key cellular anabolic reaction may indicate a link between prebiotic chemistry and the nature of the first metabolic enzymes.T he metabolic network is a large cellular system that generates life's building blocks including amino acids, nucleotides, and lipids. Most of the metabolic pathways that participate in this network are well understood, but their evolutionary origin remains an unsolved problem. The network contains many reactive and unstable intermediates, yet its topological organization is widely conserved and considered ancient. It has therefore been extensively debated to what extent this structure could be the result of Darwinian selection and thus be of postgenetic origin or whether the metabolic network topology dates back to a nonenzymatic chemistry (1-4). A series of recently discovered chemical networks provide evidence for the latter. In the presence of simple inorganic ions as found in Archean sediment, and under conditions that are reminiscent of the chemistry that operates in cells, nonenzymatic reactions replicate essential topological elements of the most central metabolic pathways. Nonenzymatic chemical reactions currently replicate glycolysis (including the EmbdenMeyerhof-Parnas pathway, the Entner-Doudoroff pathway, and their many variants), the pentose phosphate pathway, the catabolic reactions of the TCA cycle, and the formation of the methyl group donor S-adenosylmethionine (5-8). Moreover, reactions of glycolysis and the pentose phosphate pathway, as well as reactions replicating the oxidative TCA cycle, can each occur in distinct but unifying reaction milieus, respectively. This implies that simple inorganic catalysts were shaping the topological structure of the metabolic network. In other words, the reactions that sugar phosphates undergo in the presence of the highest concentrated transition metal in Archean sediment [Fe(II)] and the reactions that TCA intermediates undergo in the presence of sulfate radicals are reflected i...

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Section: Discussionmentioning

confidence: 99%

Nonenzymatic gluconeogenesis-like formation of fructose 1,6-bisphosphate in ice

Messner

Driscoll

Piedrafita

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…They include the formation of dinucleotides from adenosine 2 0 ,3 0 -cyclic phosphate (Renz et al 1971), synthesis of polynucleotides from imidazole-activated mononucleotides (Kanavarioti et al 2001;Trinks et al 2005), formation of metastable duplexes from RNA hairpins (Sun et al 2007), and extension of RNA primers by an in vitro selected ribozyme (Attwater et al 2010). Studies on the hairpin ribozyme (HPR) showed that freezing can induce self-ligation, as well as trans-ligation of RNA fragments in the absence of divalent cations (Kazakov et al 1998(Kazakov et al , 2006Vlassov et al 2004).…”

Section: Introductionmentioning

confidence: 98%

Ligation of RNA Oligomers by the Schistosoma mansoni Hammerhead Ribozyme in Frozen Solution

et al. 2016

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The interstitial liquid phase within frozen aqueous solutions is an environment that minimizes RNA degradation and facilitates reactions that may have relevance to the RNA World hypothesis. Previous work has shown that frozen solutions support condensation of activated nucleotides into RNA oligomers, RNA ligation by the hairpin ribozyme, and RNA synthesis by a RNA polymerase ribozyme. In the current study, we examined the activity of a hammerhead ribozyme (HHR) in frozen solution. The Schistosoma mansoni hammerhead ribozyme, which predominantly cleaves RNA, can ligate its cleaved products (P1 and P2) with yields up to ~23 % in single turnover experiments at 25 °C in the presence of Mg(2+). Our studies show that this HHR ligates RNA oligomers in frozen solution in the absence of divalent cations. Citrate and other anions that exhibit strong ion-water affinity enhanced ligation. Yields up to 43 % were observed in one freeze-thaw cycle and a maximum of 60 % was obtained after several freeze-thaw cycles using wild-type P1 and P2. Truncated and mutated P1 substrates were ligated to P2 with yields of 14-24 % in one freeze-thaw cycle. A pool of P2 substrates with mixtures of all four bases at five positions were ligated with P1 in frozen solution. High-throughput sequencing indicated that 70 of the 1024 possible P2 sequences were represented in ligated products at 1000 or more read counts per million reads. The results indicate that the HHR can ligate a range of short RNA oligomers into an ensemble of diverse sequences in ice.

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“…This makes sense theoretically, because cold water and ice are ideal preconditions for RNA chemistry (Vlassov et al, 2004;Attwater et al, 2010;Yarus, 2012;Lehman, 2013), which facilitates nucleotide pairing and stabilizes RNA structures which otherwise would be destroyed.…”

Section: Infectious Parasite Lifestyle Results In Immune Systemsmentioning

confidence: 99%

Crucial steps to life: From chemical reactions to code using agents

Witzany¹

2016

Biosystems

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a b s t r a c tThe concepts of the origin of the genetic code and the definitions of life changed dramatically after the RNA world hypothesis. Main narratives in molecular biology and genetics such as the "central dogma," "one gene one protein" and "non-coding DNA is junk" were falsified meanwhile. RNA moved from the transition intermediate molecule into centre stage. Additionally the abundance of empirical data concerning nonrandom genetic change operators such as the variety of mobile genetic elements, persistent viruses and defectives do not fit with the dominant narrative of error replication events (mutations) as being the main driving forces creating genetic novelty and diversity. The reductionistic and mechanistic views on physico-chemical properties of the genetic code are no longer convincing as appropriate descriptions of the abundance of non-random genetic content operators which are active in natural genetic engineering and natural genome editing.

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Ice as a protocellular medium for RNA replication

Cited by 144 publications

References 50 publications

Nonenzymatic gluconeogenesis-like formation of fructose 1,6-bisphosphate in ice

Nonenzymatic gluconeogenesis-like formation of fructose 1,6-bisphosphate in ice

Ligation of RNA Oligomers by the Schistosoma mansoni Hammerhead Ribozyme in Frozen Solution

Crucial steps to life: From chemical reactions to code using agents

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