Non-enzymatic Methylation of Cytosine in RNA by S-adenosylmethionine and Implications for the Evolution of Translation

Abstract

The non-enzymatic methylation of cytosine (C) to form 5-methylcytosine (5-mC) in deoxyribonucleic acid (DNA) by the intracellular methyl group donor S-adenosylmethionine (SAM), resulting in S-adenosylhomocysteine (SAH) and minor thymine (T) via spontaneous deamination, implicated in certain point mutagenic cancers, has been widely known since the 1980s, as has the proposed Watson-Crick mechanism of the adenine (A) moiety of SAM base-pairing with T or uracil (U). Such analogous base-pairing and non-enzymatic methylation in ribonucleic acid (RNA), however, has not been as widely addressed, particularly with respect to the origins and evolution of the process of translation initiation in the context of the hypothesized RNA world that preceded the current DNA-protein world. It is posited here, with spectrophotometric evidence put forth, that such base-pairing and non-enzymatic methylation with subsequent deamination in RNA may constitute a rudimentary form of metabolism and self-replication with implications for the origins and evolution of translation initiation, possibly including the origin and evolution of the transfer RNA (tRNA) molecule.