Dynamics of tRNA dissociation in early and later cycles of translation elongation by the ribosome

Abstract

Deacylated tRNA dissociation from E site and aminoacyl-tRNA binding to the A site of the ribosome play a critical role in repetitive cycles of protein synthesis. Available experimental data showed that in the small range of aminoacyl-tRNA concentrations, during the first few cycles of translation elongation (initiation phase of translation) the E-site tRNA can be dissociated either before or after the A-site tRNA binding, while during the later cycles of elongation (elongation phase) the E-site tRNA is mostly dissociated before the A-site tRNA binding. Here, based on our proposed model of translation elongation we study analytically the dynamics of the E-site tRNA dissociation and A-site tRNA binding, providing quantitative explanations of the available experimental data in both the initiation and elongation phases. In our model there exist two routes of state transitions within an elongation cycle in the initiation phase, with each route having stochastic E-site tRNA dissociation but with different dissociation rates. Thus, the E-site tRNA dissociation is governed by a stochastic competition between the tRNA dissociation and A-site tRNA association reactions, although in the small range of aminoacyl-tRNA concentrations used in the experiments it seems that such stochastic competition does not exist. Moreover, the detailed comparisons between the dynamics of tRNA dissociation in the initiation phase and that in the elongation phase are made.

Keywords: Elongation phase; Initiation phase; Molecular machine; Ribosome; Translation.