Ribosome stalling triggers no-go decay (NGD) and ribosome-associated quality control (RQC) pathways to rapidly degrade the aberrant mRNA and the incomplete nascent peptide, respectively. Two recent studies in yeast and mammalian systems reveal the importance of stalling-induced ribosomal protein ubiquitination by Hel2/ZNF598 for both NGD and RQC The studies also structurally explain how collided ribosomes generate a unique interface not present in monosomes, which can be recognized by Hel2/ZNF598 ubiquitin ligases.
Ribosome stalling triggers no-go decay (NGD) and ribosome-associated quality control (RQC) pathways to rapidly degrade the aberrant mRNA and the incomplete nascent peptide, respectively. Two recent studies in yeast and mammalian systems reveal the importance of stalling-induced ribosomal protein ubiquitination by Hel2/ZNF598 for both NGD and RQC The studies also structurally explain how collided ribosomes generate a unique interface not present in monosomes, which can be recognized by Hel2/ZNF598 ubiquitin ligases.
Ribosome stalling triggers quality control pathways targeting the mRNA (NGD: no-go decay) and the nascent polypeptide (RQC: ribosome-associated quality control). RQC requires Hel2-dependent uS10 ubiquitination and the RQT complex in yeast. Here, we report that Hel2-dependent uS10 ubiquitination and Slh1/Rqt2 are crucial for RQC and NGD induction within a di-ribosome (disome) unit, which consists of the leading stalled ribosome and the following colliding ribosome. Hel2 preferentially ubiquitinated a disome over a monosome on a quality control inducing reporter mRNA in an in vitro translation reaction. Cryo-EM analysis of the disome unit revealed a distinct structural arrangement suitable for recognition and modification by Hel2. The absence of the RQT complex or uS10 ubiquitination resulted in the elimination of NGD within the disome unit. Instead, we observed Hel2-mediated cleavages upstream of the disome, governed by initial Not4-mediated monoubiquitination of eS7 and followed by Hel2-mediated K63-linked polyubiquitination. We propose that Hel2-mediated ribosome ubiquitination is required both for canonical NGD (NGDRQC+) and RQC coupled to the disome and that RQC-uncoupled NGD outside the disome (NGDRQC-) can occur in a Not4-dependent manner.
Ribosome stalling triggers no-go decay (NGD) and ribosome-associated quality control (RQC) pathways to rapidly degrade the aberrant mRNA and the incomplete nascent peptide, respectively. Two recent studies in yeast and mammalian systems reveal the importance of stalling-induced ribosomal protein ubiquitination by Hel2/ZNF598 for both NGD and RQC The studies also structurally explain how collided ribosomes generate a unique interface not present in monosomes, which can be recognized by Hel2/ZNF598 ubiquitin ligases.
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| Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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| Site | Modification | Modifier | Source | Reference |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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| Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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| Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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