RNA catalysis moving towards metabolic reactions: progress with ribozyme catalyzed alkyl transfer

The RNA world hypothesis proposes that the early stages of the emergence of life on Earth comprised primitive cells in which RNA acted both to store genetic information and catalyze chemical reactions as RNA enzymes (ribozymes). Most contemporary ribozymes catalyze phosphoryl transfer reactions, but early ribozymes would have been required to catalyze a broader range of metabolic interconversions. None has been found in modern cells, yet ribozymes have been generated by in vitro evolution to catalyze several different chemical reactions, providing proof of principle of RNA-catalyzed metabolism. Recently, several different ribozymes that accelerate methyl or alkyl transfer have been isolated. As we discuss here, one of these, MTR1, uses a remarkably sophisticated catalytic mechanism involving nucleobase-mediated general acid catalysis.