Stochastic theory of protein synthesis and polysome: Ribosome profile on a single mRNA transcript

The process of polymerizing a protein by a ribosome, using a messenger RNA (mRNA) as the corresponding template, is called translation. Ribosome may be regarded as a molecular motor for which the mRNA template serves also as the track. Often several ribosomes may translate the same (mRNA) simultaneously. The ribosomes bound simultaneously to a single mRNA transcript are the members of a polyribosome (or, simply, polysome). Experimentally measured polysome profile gives the distribution of polysome sizes. Recently a breakthrough in determining the instantaneous positions of the ribosomes on a given mRNA track has been achieved and the technique is called ribosome profiling ( Ingolia et al., 2009 and Guo et al., 2010). Motivated by the success of these techniques, we have studied the spatio-temporal organization of ribosomes by extending a theoretical model that we have reported elsewhere (Sharma and Chowdhury, 2011). This extended version of our model incorporates not only (i) mechano-chemical cycle of individual ribomes, and (ii) their steric interactions, but also (iii) the effects of (a) kinetic proofreading, (b) translational infidelity, (c) ribosome recycling, and (d) sequence inhomogeneities. The theoretical framework developed here will serve in guiding further experiments and in analyzing the data to gain deep insight into various kinetic processes involved in translation.

► Our model of translation captures the largest number of features of the mechano-chemical cycle of individual ribosomes. ► We model ribosome recycling assuming a simple, but realistic, prescription. ► Our model incorporates inter-ribosome steric interactions on a mRNA transcript. ► We also explore the effects of sequence inhomoneity of the mRNA. ► Our new predictions can be tested using the recently developed “ribosome profiling” technique.