Structural basis for clearing of ribosome collisions by the RQT complex

Ribosome collisions serve as proxy for aberrant translation to initiate rescue and quality control pathways. Here, authors elucidate the molecular mechanism of collided ribosome clearance by the ribosome quality control trigger complex. Translation of aberrant messenger RNAs can cause stalling of ribosomes resulting in ribosomal collisions. Collided ribosomes are specifically recognized to initiate stress responses and quality control pathways. Ribosome-associated quality control facilitates the degradation of incomplete translation products and requires dissociation of the stalled ribosomes. A central event is therefore the splitting of collided ribosomes by the ribosome quality control trigger complex, RQT, by an unknown mechanism. Here we show that RQT requires accessible mRNA and the presence of a neighboring ribosome. Cryogenic electron microscopy of RQT-ribosome complexes reveals that RQT engages the 40S subunit of the lead ribosome and can switch between two conformations. We propose that the Ski2-like helicase 1 (Slh1) subunit of RQT applies a pulling force on the mRNA, causing destabilizing conformational changes of the small ribosomal subunit, ultimately resulting in subunit dissociation. Our findings provide conceptual framework for a helicase-driven ribosomal splitting mechanism.

Automated summary

Ribosome collisions can initiate rescue and quality control pathways for aberrant translation. The authors of this study unravel the molecular mechanism of collided ribosome clearance by the ribosome quality control trigger complex. Stalling of ribosomes due to translation of aberrant messenger RNAs can lead to ribosomal collisions. Specifically recognized collided ribosomes initiate stress responses and quality control pathways. Core to this process is the splitting of collided ribosomes by the ribosome quality control trigger complex, RQT, through an unknown mechanism. Cryogenic electron microscopy reveals that RQT engages with the 40S subunit of the lead ribosome and can adopt two conformations. The Ski2-like helicase 1 (Slh1) subunit of RQT is proposed to exert a pulling force on the mRNA, resulting in destabilizing conformational changes of the small ribosomal subunit and subsequent subunit dissociation. These findings provide a conceptual framework for a helicase-driven ribosomal splitting mechanism.