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TitleZNF574 is a Quality Control Factor For Defective Ribosome Biogenesis Intermediates.
Journal, issue, pagesbioRxiv, Year 2024
Publish dateApr 29, 2024
AuthorsJared Akers / Adrian Bothe / Hanna Suh / Carmen Jung / Zachary Stolp / Tanushree Ghosh / Liewei Yan / Yuming Wang / Tarabryn Grismer / Andreas Reyes / Tianyi Hu / Shouling Xu / Nenad Ban / Kamena Kostova
PubMed AbstractEukaryotic ribosome assembly is an intricate process that involves four ribosomal RNAs, 80 ribosomal proteins, and over 200 biogenesis factors that take part in numerous interdependent steps. This ...Eukaryotic ribosome assembly is an intricate process that involves four ribosomal RNAs, 80 ribosomal proteins, and over 200 biogenesis factors that take part in numerous interdependent steps. This complexity creates a large genetic space in which pathogenic mutations can occur. Dead-end ribosome intermediates that result from biogenesis errors are rapidly degraded, affirming the existence of quality control 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 novel quality control pathway, which we term the Ribosome Assembly Surveillance Pathway (RASP). Loss of ZNF574 results in the accumulation of faulty biogenesis intermediates that interfere with global ribosome production, further emphasizing the role of RASP in protein homeostasis and cellular health.
External linksbioRxiv / PubMed:38746087 / PubMed Central
MethodsEM (single particle)
Resolution2.59 Å
Structure data

51452

9gmo

EMDB-51452, PDB-9gmo:
eIF6-bound pre-60S large ribosomal subunit incorporating mutant uL16
Method: EM (single particle) / Resolution: 2.59 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-K:
Unknown entry

ChemComp-NA:
Unknown entry

ChemComp-GTP:
GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying molecule*YM

ChemComp-EPE:
4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID / pH buffer*YM

ChemComp-ZN:
Unknown entry

ChemComp-HOH:
WATER

Source
  • homo sapiens (human)
KeywordsRIBOSOME / Complex / pre-60S / uL16

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