RNA: Prebiotic Product, or Biotic Invention?

Abstract

Spectacular advances in structural and molecular biology have added support to the 'RNA world' hypothesis, and provide a mandate for chemistry to explain how RNA might have been generated prebiotically on the early earth. Difficulties in achieving a prebiotically plausible synthesis of RNA, however, have led many to ponder the question posed in the title of this paper. Herein, we review recent experimental work on the assembly of potential RNA precursors, focusing on methods for stereoselective C-C bond construction by aldolisation and related processes. This chemistry is presented in the context of a broader picture of the potential constitutional self-assembly of RNA. Finally, the relative accessibility of RNA and alternative nucleic acids is considered.

Ribonucleotides

“…2) (in ongoing work on the prebiotic synthesis of purine nucleotides, the systems chemistry of mixtures containing hydrogen cyanide, is additionally being investigated). However, we have not presumed a particular order of assembly, and have systematically investigated many options over the last decade or so (Sutherland and Whitfield 1997;Ingar et al 2003;Smith et al 2004;Smith and Sutherland 2005;Anastasi et al 2007Anastasi et al , 2008. Furthermore, aware of the potential for certain molecules to act as catalysts of reactions in which other molecules are joined, an important aspect of our approach has been the study of the chemistry of multicomponent chemical systems, including mixed oxygenous and nitrogenous chemistry (Szostak 2009).…”

Intercalation as a means to suppress cyclization and promote polymerization of base-pairing oligonucleotides in a prebiotic world

“…The ability of RNA to catalyze reactions is exemplified by natural and artificial ribozymes that promote a wide variety of chemical reactions (4) as well as the observation that the catalytic core of the ribosome is comprised of RNA (5). Despite the attractiveness of the RNA world as a hypothetical stage of early life, it remains unclear how RNA [or a predecessor of RNA (6-11)] would initially have been synthesized without the aid of protein enzyme catalysis.Several distinct proposals have been presented for the abiotic origin of the first RNA polymers (10,(12)(13)(14)(15)(16)(17). Perhaps the most notable is that of Ferris and coworkers, in which mineral surfaces are used to locally concentrate and promote the polymerization of ligation-activated mononucleotides, an approach that allows formation of single-stranded RNA strands up to ca.…”

“…Several distinct proposals have been presented for the abiotic origin of the first RNA polymers (10,(12)(13)(14)(15)(16)(17). Perhaps the most notable is that of Ferris and coworkers, in which mineral surfaces are used to locally concentrate and promote the polymerization of ligation-activated mononucleotides, an approach that allows formation of single-stranded RNA strands up to ca.…”

An alternative to the RNA World Hypothesis

“…A number of somewhat simpler RNA-type polymers have been synthesized. 18,19 In all cases the purines and pyrimidines are retained for base pairing purposes and the polymer backbone is altered. Implicit in these syntheses is the notion that RNA was produced from simpler polymers as the result of an evolutionary process Such a concept opens what Orgel calls a Pandora's box, because there is no way of knowing the structures of the evolutionary predecessors, and therefore the origin of life from an RNA world point of view becomes opaque.…”