Molecular Highway Patrol for Ribosome Collisions

During translation, messenger RNAs (mRNAs) are decoded by ribosomes which can stall for various reasons. These include chemical damage, codon composition, starvation, or translation inhibition. Trailing ribosomes can collide with stalled ribosomes, potentially leading to dysfunctional or toxic proteins. Such aberrant proteins can form aggregates and favor diseases, especially neurodegeneration. To prevent this, both eukaryotes and bacteria have evolved different pathways to remove faulty nascent peptides, mRNAs and defective ribosomes from the collided complex. In eukaryotes, ubiquitin ligases play central roles in triggering downstream responses and several complexes have been characterized that split affected ribosomes and facilitate degradation of the various components. As collided ribosomes signal translation stress to affected cells, in eukaryotes additional stress response pathways are triggered when collisions are sensed. These pathways inhibit translation and modulate cell survival and immune responses. Here, we summarize the current state of knowledge about rescue and stress response pathways triggered by ribosome collisions. The discovery of ribosome collisions as the recognition platform of translation problems caused by various factors represents a cornerstone in the field of translation surveillance. We summarize our current knowledge about the pathways that target collided ribosomes. These pathways do so directly ‐ by removing or recycling ribosomes, peptides, and mRNA ‐ or indirectly ‐ by modulating translation and cellular fate.