Fig. 6: Ribosome traffic jams underlie suppression between inhibition of translocation and initiation.

a Schematic of ribosomes progressing along a transcript—a stuck ribosome can cause a traffic jam. Ribosomes undergo factor-mediated initiation events with attempt rate ζ and translocation with attempt rate γ. Expression of initiation and elongation factors are controlled by the level of inducer (IPTG and aTc, respectively). b Results of all-or-nothing growth assay: bacteria grow only when both essential factors are induced. c Left: measured growth rate response surface for the dual inducible promoter strain from (a) as a function of both inducer concentrations; the red line shows the ridge of maximum growth. Right: cross-section of the response surface along the dashed purple line (gray circles) and at maximal aTc induction (white circles); solid lines are smoothed profiles. Black arrow denotes a decrease in translocation; if initiation is lowered simultaneously with translocation (orange arrow), growth reduction is smaller. d Schematic of the theoretical model: translation is described as an ensemble of transcripts competing for the limited and growth-rate-dependent pool of ribosomes. Ribosomes advance on transcripts as described by a generalized totally asymmetric simple exclusion process (TASEP) for particles of size L (see a and text). When γ < ζ(1 + L^1/2), ribosomes saturate and traffic jams develop, resulting in a drop in elongation and growth (black arrow, the transition happens at the black triangle) (Supplementary Methods^59,60,). When ζ < γ/(1 + L^1/2), a phase transition occurs (green triangle): traffic jams dissolve—elongation and growth increase (along the green arrow). e Left: the growth rate predicted by the generalized TASEP model recapitulates suppression of translocation inhibition by lowered initiation; note that, unlike in (c), axes show the concentrations of translation factors. States below and to the right of the green line are in the translocation limiting regime. Right: cross-sections of the response surface. As the initiation factor level is decreased, the critical point of the phase transition (green triangle) is reached; growth starts increasing after passing the critical point, and decreases again after passing the maximum (red square) as the number of translating ribosomes becomes limiting. f Bottleneck dependency (BD) score quantifies the deviation from independent expectation (BD = 0) for the response surfaces in (c, e); heights of bars corresponds to the medians and error bars are 90% bootstrap confidence intervals. Medians and confidence intervals were estimated from n = 100 bootstrap data points.