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Register a new userA biologically motivated three-species exclusion model: effects of leaky scanning and overlapping genes on initiation of protein synthesis
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Added by
Debashish Chowdhury
Publication date
2018
fields
Physics
and research's language is
English
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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, pre-fabricated, 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 {it 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.
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We develope a theoretical framework, based on exclusion process, that is motivated by a biological phenomenon called transcript slippage (TS). In this model a discrete lattice represents a DNA strand while each of the particles that hop on it unidirectionally, from site to site, represents a RNA polymerase (RNAP). While walking like a molecular motor along a DNA track in a step-by-step manner, a RNAP simultaneously synthesizes a RNA chain; in each forward step it elongates the nascent RNA molecule by one unit, using the DNA track also as the template. At some special slippery position on the DNA, which we represent as a defect on the lattice, a RNAP can lose its grip on the nascent RNA and the latters consequent slippage results in a final product that is either longer or shorter than the corresponding DNA template. We develope an exclusion model for RNAP traffic where the kinetics of the system at the defect site captures key features of TS events. We demonstrate the interplay of the crowding of RNAPs and TS. A RNAP has to wait at the defect site for longer period in a more congested RNAP traffic, thereby increasing the likelihood of its suffering a larger number of TS events. The qualitative trends of some of our results for a simple special case of our model are consistent with experimental observations. The general theoretical framework presented here will be useful for guiding future experimental queries and for analysis of the experimental data with more detail
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The generation of two non-identical membrane compartments via exchange of vesicles is considered to require two types of vesicles specified by distinct cytosolic coats that selectively recruit cargo and two membrane-bound SNARE pairs that specify fusion and differ in their affinities for each type of vesicles. The mammalian Golgi complex is composed of 6-8 non-identical cisternae that undergo gradual maturation and replacement yet features only two SNARE pairs. We present a model that explains how the distinct composition of Golgi cisternae can be generated with two and even a single SNARE pair and one vesicle coat. A decay of active SNARE concentration in aging cisternae provides the seed for a cis > trans SNARE gradient that generates the predominantly retrograde vesicle flux which further enhances the gradient. This flux in turn yields the observed inhomogeneous steady-state distribution of Golgi enzymes, which compete with each other and with the SNAREs for incorporation into transport vesicles. We show analytically that the steady state SNARE concentration decays exponentially with the cisterna number. Numerical solutions of rate equations reproduce the experimentally observed SNARE gradients, overlapping enzyme peaks in cis, medial and trans and the reported change in vesicle nature across Golgi: Vesicles originating from younger cisternae mostly contain Golgi enzymes and SNAREs enriched in these cisternae and extensively recycle through the Endoplasmic Reticulum (ER), while the other subpopulation of vesicles contains Golgi proteins prevalent in older cisternae and hardly reaches the ER.
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We present a study of exclusion processes on networks as models for complex transport phenomena and in particular for active transport of motor proteins along the cytoskeleton. We argue that active transport processes on networks spontaneously develop density heterogeneities at various scales. These heterogeneities can be regulated through a variety of multi-scale factors, such as the interplay of exclusion interactions, the non-equilibrium nature of the transport process and the network topology. We show how an effective rate approach allows to develop an understanding of the stationary state of transport processes through complex networks from the phase diagram of one single segment. For exclusion processes we rationalize that the stationary state can be classified in three qualitatively different regimes: a homogeneous phase as well as inhomogeneous network and segment phases. In particular, we present here a study of the stationary state on networks of three paradigmatic models from non-equilibrium statistical physics: the totally asymmetric simple exclusion process, the partially asymmetric simple exclusion process and the totally asymmetric simple exclusion process with Langmuir kinetics. With these models we can interpolate between equilibrium (due to bi-directional motion along a network or infinite diffusion) and out-of-equilibrium active directed motion along a network. The study of these models sheds further light on the emergence of density heterogeneities in active phenomena.
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