Structure and Function of Aminoacyl-tRNA Synthetase Ribozyme
Hiroaki Suga Principal Investigator
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9982237<br/>Suga <br/>There is the hypothesis that coded protein synthesis evolved from a set of ribozyme catalyzed acyl-transfer reactions, including aminoacyl-tRNA synthetase (ARS) ribozymes. This PI has recently succeeded in isolating a novel ribozyme capable of synthesizing aminoacyl-tRNA. This ribozyme is able to specifically recognize an activated glutaminyl ester and aminoacylate a targeted tRNA via a covalent aminoacyl-ribozyme intermediate. We refer to this type of ribozymes as ARS ribozymes, and to those specific to glutamine as GlnRS ribozymes. Our most recent progress in the evolution of a GlnRS ribozyme clone has provided a promising route for the generation of highly active and specific ribozymes to selected amino acids. The PI proposes to conduct extensive studies on the GlnRS ribozyme to gain insights into its structure-function relationship. The studies involve the combination of biochemical methods, computer simulation, and X-ray crystallographic approach. These studies will reveal not only catalytic mechanism and higher-order structure of the ribozyme but also increase our understanding of RNA catalysis and structure in general. The outcome of this research may also provide an important implication for possible roles of ribozymes in the evolution of the genetic translation system that might have occurred in the RNA world. Furthermore, this information will be essential in the development of a novel and practical catalytic RNA system for the synthesis of non-natural aminoacyl-tRNAs. Successful development of such system will drive future directions of our long-term goal, a cell-free in vitro translation system composed of ARS ribozymes, which facilitates engineering and evolution of proteins containing non-natural amino acids.