Aberrant translation causes ribosome stalling, which leads to the ubiquitination of ribosomal proteins and induces ribosome-associated quality control. As part of this quality control process, the E3 ubiquitin ligase RNF10 monoubiquitinates ribosomal protein RPS3. Here, we demonstrate that RNF10-mediated RPS3 monoubiquitination antagonizes ribosomal half-mer formation by promoting dissociation of 40S subunits from ribosomes stalled during translation elongation. Interestingly, RNF10 …