Nonenzymatic RNA Oligomerization at the Mineral–Water Interface: An Insight into the Adsorption–Polymerization Relationship

Abstract

Nonenzymatic RNA polymerization, a major challenge in understanding the origins of life on early Earth, was previously achieved in the presence of montmorillonite clay and high magnesium concentrations (∼75 mM), but the molecular interactions promoting ribonucleotide oligomerization remain unknown. High adsorption capacity of minerals is generally assumed to favor polymerization efficiency; however, this relationship was never shown. Here we examined the relationship between ribonucleotide adsorption affinity and the role of magnesium in the polymerization catalytic efficiency of minerals. Results showed that adsorption of the activated mononucleotide, 2-methylimadzolide of adenosine monophosphate (2-MeImPA), is approximately 10 times higher on zincite (ZnO) than on montmorillonite clay, but only montmorillonite acts as a catalyst for 2-MeImPA polymerization. In the presence of montmorillonite, oligomers formed even in pure water without any salts present. Attenuated total reflectance FTIR and cross-polarization-magic angle spinning 31 P NMR spectroscopy showed that 2-MeImPA mononucleotides adsorption on ZnO directly involves the phosphate moiety, making it unavailable for polymerization. In contrast, mononucleotides adsorbed on montmorillonite by weak amine interactions leaving the phosphate moiety available for polymerization. Thus, providing a favorable orientation of the monomer, rather than a high adsorption capacity, as well as providing a nanoconfined environment and outer-sphere complex formation with the nucleotide are requisite properties for a mineral to be catalytic to nucleotide polymerization.

The Hot Spring Hypothesis for an Origin of Life

“…As described earlier, biological polymers such as oligonucleotides and oligopeptides are products of condensation reactions and can be synthesized when their solutions are exposed to multiple wet-dry cycles in acidic fresh water (Rajamani et al, 2008;Toppozini et al, 2013;da Silva et al, 2014;DeGuzman et al, 2014;Forsythe et al, 2015;Rodriguez-Garcia et al, 2015;Himbert et al, 2016;Misuraca et al, 2017;Yu et al, 2017). Mineral surfaces and peptides may play roles such as nonenzymatic polymerization in early steps in life's origins and bear further investigation (Dalai and Sahai, 2018;Kaddour et al, 2018). If lipids are present during a wet-dry cycle, polymers are encapsulated to form protocells (Deamer and Barchfeld, 1982;Apel et al, 2002).…”

Amino Acid Specific Nonenzymatic Montmorillonite‐Promoted RNA Polymerization

“…The condensation reactions needed for the formation of RNA phosphodiester bonds are not thermodynamically favorable in aqueous solutions. To circumvent this, microenvironments, such as mineral surfaces, [8] lipid surfaces [9] or water‐ice eutectic phases [10] have been used to facilitate condensation reactions [11,12] . RNA polymerization by nonenzymatic template‐directed primer extension has been achieved but requires high (∼80 mM) concentrations of Mg 2+ and the question remains as to where the primer or template came from.…”

“…Montmorillonite clay facilitates the non-enzymatic polymerization of activated mononucleotides. [8,[12][13][14][15][16][17] Effects of various salt-exchanged clays, background electrolyte ions, pH values, minerals, nucleotides and activating groups were examined on the efficiency, [15,[18][19][20][21][22] regioselectivity [15,[23][24][25] and chiral selectivity [26] of the polymerization reaction.…”

Lipid-Assisted Polymerization of Nucleotides

“…Although, initial work did not provide high yields for these reactions [11], later work from Ferris and colleagues demonstrated that minerals such as montmorillonite could provide a suitable surface upon which nucleotides could adsorb, favoring their efficient oligomerization [12]. This is a line that researchers are continuing to pursue even to date [13]. Some researchers have also studied the protective effect of minerals that protect RNA from degradation [14].…”

“…The effect of minerals can also go beyond mere protection of the RNA molecules from degradation by hydrolysis. In fact, Kaddour et al [13] tested the hypothesis of whether better adsorption of monomers on mineral surfaces would indeed favor increased polymerization. They showed that although adsorption of activated mononucleotide, 2-methylimadzolide of adenosine monophosphate (2-MeImPA), is approximately 10 times higher on zincite (ZnO) than on montmorillonite clay, only montmorillonite acts as a catalyst for 2-MeImPA polymerization.…”