Contribution of tRNA Met core flexibility to aminoacylation

Abstract

The fidelity of protein synthesis is largely dominated by the correct recognition of transfer RNAs (tRNAs) by their cognate aminoacyl-tRNA synthetases (AARSs). Aminoacylation of each tRNA with its cognate amino acid is necessary to maintain the fidelity of the genetic code. Methionyl-tRNA synthetase (MetRS) aminoacylates both initator and elongator tRNAMet species for protein synthesis; the methionine-specifying CAU anticodon is a key contributor to tRNAMet identify. The communication between tRNAMet and MetRS is not well understood. We hypothesize that the core of tRNAMet is involved in dynamic communication between the tRNA anticodon and acceptor ends, and that such communication contributes to the rearrangement of the tRNA 3′-end to fit into the enzyme active site. Using both experimental and computational approaches, the effects of single nucleotide substitutions in the tRNAMet core and the impact they have on tRNA structure and function will be investigated.