Figure 7.

Model for Recognition of Aberrant Translation by ZNF598

(A) ZNF598 does not engage ribosomes that are translating normally or slow down at a difficult-to-translate sequence (regional slowdown). If the relative velocities of the lead and trailing ribosomes permit the trailing ribosome to close the inter-ribosomal distance (IRD) before the slowed ribosome moves 10 codons away, a collision will occur to allow recognition by ZNF598.

(B) Heatmap of the collision probability for a given slowdown (x axis) as a function of the distance to the trailing ribosome (y axis). An average velocity for the trailing ribosome of 5.6 ± 2.5 codons per second was used. At the genome-wide average IRD of 66 codons (∼200 nt), appreciable collisions will not occur unless the lead ribosome slows to ∼1 codon per second (less than one-fifth the normal rate) over a 10-codon stretch. However, for very frequently initiated mRNAs that have a very short IRD (such as globin mRNA), a mere 2-fold slowdown is sufficient to begin observing collisions.