FIG 2.
Ribosome trafficking model. (a) Schematic description of the ribosome trafficking model. Free ribosomes may initiate translation at the rate kinit if the start codons of mRNAs are not occupied. Every translating ribosome may bind a charged cognate tRNA at the rate kchc, where c is the charging level of the tRNA, and elongate one codon at the rate kel (1); bind an uncharged cognate tRNA, eject, and produce (p)ppGpp (increase the RelA activity by 1 unit) at the rate kunu, where u = 1 − c gives the uncharged level (2); or abort translation at the rate pabort (3). We also allowed for noncognate tRNA binding to ribosomal A sites at the small rate pmistrl to represent mistranslation. Elongation occurs only if the codon in front is free. Translation is terminated when a ribosome finishes translating all the codons and exits the mRNA. A detailed description of the algorithm is available in Materials and Methods. (b) Ribosome occupancy on mRNA. (Left) Spatiotemporal plot of ribosome traffic on a randomly generated mRNA upon isoleucine starvation at time zero. The lines represent the movement of ribosomes. The blue lines represent normal translation, and the red lines represent (p)ppGpp synthesis. (Right) Relative mean occupancies of mRNA codons by ribosomes in the poststarved steady state. The dashed lines represent the locations of isoleucine codons. (c) Relative RelA activities (η) in the pre- and poststarved states. The averages for 100 independent simulations were plotted as a red curve. The dashed line represents the induction time of starvation. (d) The level of isoleucine starvation was modulated by sampling the uncharged level of tRNAIle (uIle) between 0 and 1. The relative RelA activities (η) in the poststarved steady state were plotted. The figure confirms the previous claim that the stringent response is significant when more than 85% of tRNAs are uncharged (53).