Abstract

There are currently two main schools of thought regarding the origins of RNA. In one school, RNA is considered to be a product of nonenzymatic, prebiotic reactions. In the other, RNA is considered to be a product of chemical and/or biological evolution. The numerous challenges to demonstrating a plausible prebiotic synthesis of RNA support the hypothesis that life started with an ancestral RNA-like polymer, or proto-RNA. If RNA is an “invention” of early life, then it is logical to assume that identifying the chemical structure of proto-RNA, and intermediate pre-RNAs, would require exploration of a seemingly insurmountable number of possible proto-RNA building blocks and prebiotic reactions. Here we report progress toward finding a proto-RNA that is the product of molecular self-assembly. Results obtained thus far demonstrate that seemingly minor changes to the structure of the extant building blocks of RNA (e.g., the substitution of uracil by barbituric acid) alleviate several long-standing problems associated with finding a prebiotic synthesis for RNA.