RNA scaffolds for minihelix-based aminoacyl transfer: design of "transpeptizymes"

Abstract Some evidence and considerations suggest that RNA minihelices based on the acceptor-TΨC stem-loop of tRNAs are the historical, more ancient part of the tRNA structure. These minihelices are substrates for aminoacylation by tRNA synthetases. In the transition from the RNA world to the theatre of proteins, aminoacyl minihelices may have had a role in early systems of peptide synthesis. Such systems would require bringing together aminoacyl groups into close proximity in order for peptide bonds to form. Here we report the design of RNA scaffolds based on pieces of the structure of the P4-P6 domain of the Tetrahymena ribozyme. RNA minihelices were incorporated into these scaffolds and the resulting RNAs could be enzymatically aminoacylated. The RNA scaffolds containing the minihelix-like pieces associated spontaneously to create the presumptive P4-P6 structure and thereby bring together the substrates for aminoacylation. Thus, peptide synthesis with associating RNA scaffolds that contain minihelix-like motifs appears plausible.