Expanding the Genetic Code with Phosphoserine

Yale University, New Haven CT

Investigators

Abstract

Synthesis of proteins containing amino acids outside of the genetic code has recently resurfaced as a topic of much interest and presents a great challenge intellectually and technically. Reprogramming the genetic code requires two key events: (i) The creation of a new efficient 'orthogonal' aminoacyl tRNA synthetase:tRNA pair able to generate solely a non canonical aminoacyl tRNA. (ii) The ability to specify the position in which this amino acid will be inserted in the protein by recoding a particular mRNA codon. Based on the natural existence of the recently discovered methanogen aminoacylsynthetase like protein, O-phosphoseryl tRNA synthetase and its cognate tRNACys research will be initiated to develop a prokaryotic and a eukaryotic system for the cotranslational insertion of phosphoserine at pre determined positions in a polypeptide based on the nonsense codon UAG in a messenger RNA. Given the importance of phosphoserine in eukaryotic proteins essential for cell proliferation, cellular signaling, and cell death, a robust method of making phosphoserine containing proteins will have wide application and great significance. This project will provide interdisciplinary training for undergraduate and postdoctoral students.