"Ribopepzymes" are probably a link from ribozymes to protein enzymes

Abstract

The evolutionary relationship between RNA- and protein-based biocatalysts was key to the evolution of living systems. This relationship is thought to have depended upon the transfer of both genetic information and catalytic function in living systems. We investigated whether ribozymes could transfer genetic information and catalytic function at the chemical level. We identified a family of peptides encoded by ribozymes: 13-residue peptide encoded by the hammerhead ribozyme, a 19-residue peptide encoded by the genomic hepatitis delta virus (HDV+) ribozyme, a 25-residue peptide encoded by the antigenomic HDV (HDV-) ribozyme, a 15-residue peptide encoded by the smallest trans-acting genomic HDV (SHDV) ribozyme, and a 22-residue peptide encoded by an open reading frame (ORF) of RNase P. We show that all these peptides possess the ability to cleave single-stranded RNA substrates. Furthermore, we expressed a 56-residue peptide encoded by an intact ORF (616-783) of the VS ribozyme, and found that it has single-stranded RNA cleavage activity as well. Because these catalytic peptides arise from a ribozyme-based code and their catalytic activity is ribonuclease-like, we have designated these peptides as "ribopepzymes". Ribopepzymes could be a link from ribozymes to protein enzymes in the early origin and evolution of enzymes. They also may provide a basis for designed, divergent evolution of enzyme function