Figure 3.

Schematic illustration of cellular responses triggered by ribosome collisions.

Binding of EDF1 to collided ribosomes promotes GIGYF2-4EHP-mediated inhibition of initiation of new ribosomes on the mRNA. The extent of collisions is sensed by ZAKα, which activates GCN2-mediated ISR by inhibiting cap-dependent translation and facilitating selective translation of stress response genes if the collisions are temporary and/or occur at low frequency. If ZAKα senses persistent collisions and stalled ribosomes, it activates MAP kinase cascades of RSR to promote apoptosis. See sections 2.3 and 3 in the text for details.