The long-term objective of this proposal is to understand the evolution of protein synthesis. Specifically, the proposed research is designed to date aminoacyl-RNA systems based on the acceptor stem loop of tRNAs that will allow for peptide bond formation in a noncoded fashion. This aminoacyl-RNA complex may have served as a primitive protein translation system. The genetic information encoded by RNA is translated into proteins, which are central to virtually every biochemical and structural function in cells. Accordingly, analysis of the basic process of peptide synthesis may contribute to a greater understanding of the origins of human diseases. The two strategies that will be employed to achieve the proposed goal are 1) utilize an aminoacylatable RA scaffold based on the structure of the P4-P6 tetrahymena ribozyme complex to construct peptides and 2) develop an aminoacylated RNA triple helix system consisting of a hairpin minihelix and a single-stranded ribonucleotide to generate peptides.
