The G3BP1-Family-USP10 Deubiquitinase Complex Rescues Ubiquitinated 40S Subunits of Ribosomes Stalled in Translation from Lysosomal Degradation

Jan 26, 2020Molecular cell

A protein complex helps save stalled ribosome parts tagged for breakdown from being destroyed in lysosomes

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Abstract

Knockout of USP10 or G3BP1 family proteins increased lysosomal ribosomal degradation and perturbed ribosomal subunit stoichiometry.

  • Ribosome-associated quality control (RQC) initiates with the E3 ligase ZNF598 sensing ribosome collisions.
  • Deubiquitination of ribosomal proteins RPS2, RPS3, and RPS10 requires G3BP1-family-USP10 complexes.
  • A single K214R substitution of RPS3 can rescue ribosomal degradation caused by protein knockout.
  • Most monoubiquitination of RPS2 and RPS3 is linked to ZNF598-dependent ribosome collision detection.
  • G3BP1 family proteins primarily target 40S ribosomal subunits and associated mRNAs, rather than RNA alone.

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