ZNF574 is a quality control factor for defective ribosome biogenesis intermediates.

Eukaryotic ribosome assembly is an intricate process that involves four ribosomal RNAs, 80 ribosomal proteins, and over 200 biogenesis factors that participate in numerous interdependent steps. The complexity and essentiality of this process create opportunities for deleterious mutations to occur, accumulate, and impact downstream cellular processes. "Dead-end" ribosome intermediates that result from biogenesis errors are rapidly degraded, affirming the existence of quality control (QC) pathway(s) that monitor ribosome assembly. However, the factors that differentiate between on-path and dead-end intermediates are unknown. We engineered a system to perturb ribosome assembly in human cells and discovered that faulty ribosomes are degraded via the ubiquitin-proteasome system. We identified ZNF574 as a key component of a QC pathway, which we term the ribosome assembly surveillance pathway (RASP). In an animal model, loss of ZNF574 leads to developmental defects, emphasizing the importance of RASP in organismal health.