Canary in a coal mine: collided ribosomes as sensors of cellular conditions

The recent discovery that collision of ribosomes triggers quality control and stress responses in eukaryotes has shifted the perspective of the field. Collided eukaryotic ribosomes adopt a unique structure, acting as a ubiquitin signaling platform for various response factors. While several of the signals that determine which downstream pathways are activated have been uncovered, we are only beginning to learn how the specificity for the activation of each process is achieved during collisions. This review will summarize those findings and how ribosome-associated factors act as molecular sentinels, linking aberrations in translation to the overall cellular state. Insights into how cells respond to ribosome collision events will provide greater understanding of the role of the ribosome in the maintenance of cellular homeostasis. Collision of ribosomes is the key event for quality control processes and other stress response pathways during translation.The collided di-ribosome adopts a unique structure that acts as a signaling platform for various factors.Differential ubiquitination of ribosomal proteins determines which pathways are activated and the fate of the ribosome.Ribosome quality control and the integrated stress response appear to antagonize one another’s activation.Ribosome collisions are utilized to trigger global reprogramming of gene expression in response to stress.