Abstract:

Bacteria have two class-I peptide release factors in contrast to a single release factor in eukaryotes. Among these RF2, the major release factor recognizes and cuts nascent peptide chains on the UAA and UGA stop codons, while UAG is specific for RF1. Till date, the molecular mechanisms for how RF1 and RF2 recognize their specific stop codons remained obscure.  By using a naturally evolved mutant RF2, and employing fast-kinetics biochemistry as well as high resolution cryo-EM structures, we have unraveled how RF2 recognizes specifically UAA and UGA codons. Our findings have added new mechanistic insights for translation termination.