Structure of the no-go mRNA decay complex Dom34 - Hbs1 bound to a stalled 80S ribosome

Messenger RNAs (mRNAs) that induce stalling during translation are degraded by a quality control mechanism known as no-go decay (NGD). The aberrant mRNAs are recognized by two factors, Dom34 and Hbs1. Using cryo-EM to visualize NGD intermediates bound to a stalled ribosome, Beckman and coworkers suggest how binding of Dom34-Hbs1 may lead to ribosome disassembly and recruitment of mRNA degradation factors. No-go decay (NGD) is a mRNA quality-control mechanism in eukaryotic cells that leads to degradation of mRNAs stalled during translational elongation. The key factors triggering NGD are Dom34 and Hbs1. We used cryo-EM to visualize NGD intermediates resulting from binding of the Dom34–Hbs1 complex to stalled ribosomes. At subnanometer resolution, all domains of Dom34 and Hbs1 were identified, allowing the docking of crystal structures and homology models. Moreover, the close structural similarity of Dom34 and Hbs1 to eukaryotic release factors (eRFs) enabled us to propose a model for the ribosome-bound eRF1–eRF3 complex. Collectively, our data provide structural insights into how stalled mRNA is recognized on the ribosome and how the eRF complex can simultaneously recognize stop codons and catalyze peptide release.