Eukaryotic ribosomal quality control degrades faulty ribosomal assemblies, but precise mechanisms to target defective pre-ribosomes remain unclear. Now, Akers et al. report a ribosome assembly surveillance pathway that requires the protein ZNF574.

Using the K562 lymphoblast human cell line, the authors find that mutant ribosomal protein uL16mut blocks 60S ribosome maturation; these 60Smut defective subunits are degraded during biogenesis by the ubiquitin proteasome system. Using a CRISPR interference screen, the authors identified ZNF574, predicted to interact with ribosomal proteins, as required for 60Smut degradation. ZNF574–uL16 interactions were assessed with co-immunoprecipitation and proximity ligation assays. Cryo-electron microscopy of 60Smut suggests that the peptidyl transferase centre adopts a mature conformation. The authors propose that 60Smut cannot release eIF6 as the otherwise final step of 60S maturation. ZNF574 depletion stabilizes ribosome mutants with slowed ribosome biogenesis, which suggests that ZNF574 targets stalled biogenesis intermediates. The authors found znf574−/− homozygous mutant zebrafish embryos display several morphological defects reminiscent of ribosomopathies.