Biologically motivated three-species exclusion model: Effects of leaky scanning and overlapping genes on initiation of protein synthesis

Abstract

Totally asymmetric simple exclusion process (TASEP) was originally introduced as a model for the traffic-like collective movement of ribosomes on a messenger RNA (mRNA) that serves as the track for the motor-like forward stepping of individual ribosomes. In each step, a ribosome elongates a protein by a single unit using the track also as a template for protein synthesis. But, prefabricated, functionally competent, ribosomes are not available to begin synthesis of protein; a subunit directionally scans the mRNA in search of the pre-designated site where it is supposed to bind with the other subunit and begin the synthesis of the corresponding protein. However, because of 'leaky' scanning, a fraction of the scanning subunits miss the target site and continue their search beyond the first target. Sometimes such scanners successfully identify the site that marks the site for initiation of the synthesis of a different protein. In this paper, we develop an exclusion model, with three interconvertible species of hard rods, to capture some of the key features of these biological phenomena and study the effects of the interference of the flow of the different species of rods on the same lattice. More specifically, we identify the meantime for the initiation of protein synthesis as appropriate mean first-passage time that we calculate analytically using the formalism of backward master equations. In spite of the approximations made, our analytical predictions are in reasonably good agreement with the numerical data that we obtain by performing Monte Carlo simulations. We also compare our results with a few experimental facts reported in the literature and propose new experiments for testing some of our new quantitative predictions. arXiv:1812.10143v2 [cond-mat.stat-mech]