RNA Second Messengers and Riboswitches: Relics from the RNA World?

C ompelling evidence supports the hypothesis that modern cells descended from organisms whose components were made entirely of RNA. Scientists who helped formulate this “RNA World” hypothesis for the evolution of life have identified many characteristics of modern cells that strongly suggest RNA once ruled the planet. For example, the existence of selfcleaving and self-splicing ribozymes that cut and ligate RNAs demonstrates that at least some RNA-processing reactions can be catalyzed without the need for proteins. Also, the existence of ribosomal RNAs that build all genetically encoded proteins emphasizes the fact that today’s organisms depend on RNA to carry out fundamental biochemical processes. Even many nucleotide-like coenzymes that are near universal in all life forms likely first appeared in RNA World organisms. The RNA World hypothesis is appealing because it helps explain the arcane characteristics of genetic and biochemical processes in modern cells. Why do all cells use ribosomal RNAs, and not protein enzymes, to stitch together amino acids to make polypeptides? Most likely, the ribosome’s peptidyl transferase center is an evolutionary descendent of an ancient ribozyme that first catalyzed this reaction before protein enzymes evolved. Why do so many coenzymes, such as adenosylcobalamin (AdoCbl), thiamin pyrophosphate (TPP), flavin mononucleotide (FMN), S-adenosylmethionine (SAM), molybdenum cofactor (Moco), and tetrahydrofolate (THF), all carry recognizable fragments of RNA nucleotides or derive from nucleotide precursors? Perhaps these compounds served as coenzymes for metabolic ribozymes of the RNA World, and they have been preserved as legacies from a time before protein enzymes existed. The study of RNAs and RNA-derived small molecules may shed some light on the functions that RNA carried out before proteins emerged. We can use such insights to seek functional RNAs in modern cells that Summary