ZNF574 is a Quality Control Factor Targeting Defective Ribosome Biogenesis Intermediates

The eukaryotic ribosome is a complex molecular machine responsible for the translation of mRNA to protein. Faulty ribosome production leads to decreased protein production, increased cellular stress, and often cell death. How defective ribosomes are detected and cleared is poorly understood. We modeled ribosome biogenesis failure in human cells and performed CRISPRi screens to identify quality control factors that cope with trapped biogenesis intermediates. We identified ZNF574 as the top hit. ZNF574 contains Cys2-His2 (C2H2) zinc finger binding domains that are known to interact with both DNA and RNA, providing a potential mechanism for recognizing and engaging defective ribosomes. ZNF574 localizes in the nucleoplasm and cellular speckles, similar to late ribosome biogenesis factors like eIF6 and NMD3. We confirmed that depletion of ZNF574 impedes the degradation of faulty ribosomes. We performed immunoprecipitation followed by mass spectrometric analysis. Our immunoprecipitation of GFP-tagged ZNF574 followed by mass spectrometry analysis of interacting proteins revealed strong enrichment for ribosomal proteins from the large subunit. Together, our data show that ZNF574 functions as a quality control factor that targets defective large subunits.