Peptides for RNA discrimination and for assembly of enzymes that act on RNA

RNA recognition by tRNA synthetases is thought to have arisen by the recruitment of RNA binding peptide elements into the frameworks of primordial enzymes that carried out amino acid activation. While peptides have been shown to have the capacity to discriminate irregular RNA structures such as bulges and loops, the sequence-specific recognition of base pairs in RNA helices like those in tRNAs had not been demonstrated. Such discrimination by peptide binders was thought to be inherently difficult. But in this work we show that discrimination of a single base pair in an RNA helix may be achieved with a rationally designed, chemically synthesized peptide. In a separate study, we demonstrated the noncovalent association of a peptide binder with an amino acid activation domain to give an active and specific tRNA synthetase. Thus, peptides with high specificity for an RNA helix can be obtained. In addition, a peptide can associate with another protein to give an enzyme that acts on RNA. The principles suggested by these studies may be general.