The closed-loop model of translation.

<p>Ribosomes (shaded in grey), modeled as extended particles that occupy 10 codons (black boxes), join the transcript at the start codon from the cytoplasmic pool at the <i>de novo</i> initiation rate, and hop to the next codon (in the 5' to 3' direction) at the elongation rate. Upon reaching the stop codon, ribosomes either return to the cytoplasmic pool at the release rate or return to the start codon at the reinitiation rate. The reinitiation level is determined by the reinitiation rate divided by the sum of the reinitiation and release rates. If the initiation site is occupied (i.e. any of the first 10 codons is being decoded), new ribosomes fail to join the transcript and reinitiating ribosomes either remain at the termination site or return to the cytoplasmic pool at the release rate. An elongating ribosome fails to step forward if the distance between its center and that of the ribosome in front is ≤ 10 codons (collision). Stochastic simulations were performed using the Gillespie algorithm. The Gillespie algorithm consists of multiple steps: (1) Initialization: the simulation time is set to zero; at this point in our simulations, all transcripts are empty and the only possible reaction is <i>de novo</i> initiation; (2) List all possible reactions: all possible reactions are determined and their rates are used to calculate the total rate of possible reactions; (3) Monte Carlo step: two random numbers are generated, the first determines the waiting time until the next reaction based on the total rate of possible reactions, and the second determines which reaction occurs using each reaction rate as a probabilistic weight; (4) Update: the time is increased by the randomly generated waiting time from step 3 and the chosen reaction is performed; (5) Iteration: repeat from step 2 unless the transcript lifetime has been reached.