ArticleMolecular cell2025
The integrated stress response regulates 18S nonfunctional rRNA decay in mammals.
Article in Molecular cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- 40S ribosome remodeling triggers 18S rRNA U-tailing and DIS3L2-dependent decay.Molecular cell · 2026Article
- Nucleolar reorganization on stress depends on physicochemical changes due to reduced nascent rRNA synthesis.EMBO reports · 2026Article
- Stress-induced ribosome degradation in Bacillus subtilis is mediated by the RNase Y-specificity complex.Nature communications · 2026Article
- Proteomic Profiling Reveals How Physiological Media Reshape Cancer Cell Proteomes and Signaling Networks.Molecular & cellular proteomics : MCP · 2026Article
- ZAP targets aberrant mRNA transcripts encoding proteins with defective signal peptides for degradation.The EMBO journal · 2026Article
- Crosstalk between the ribosome quality control-associated E3 ubiquitin ligases LTN1 and RNF10.FEBS letters · 2026Article
- Ribosome-associated quality control and related mechanisms.Nature structural & molecular biology · 2026Review
- How tailored Ribo-seq methods probe unique translation events.RNA (New York, N.Y.) · 2026Review
- Ribosome-associated quality control of aberrant protein production during amino acid limitation.bioRxiv : the preprint server for biology · 2026Article
- Collision-induced ribosome degradation driven by ribosome competition and translational perturbations.Nature communications · 2025Article
- Translational regulation in stress biology.Nature cell biology · 2025Review
- Comparative CRISPRi screens reveal a human stem cell dependence on mRNA translation-coupled quality control.Nature structural & molecular biology · 2025Article
- The ribosome ubiquitination code: fine-tuning translation under stress.Trends in biochemical sciences · 2025Review
- Translation stalling in neurons: a critical mechanism for timely protein delivery to distal cellular processes.Biochemical Society transactions · 2025Article
- Ribosomal RNA Degradation (RNA Disruption) in Tumour Cells: Mechanistic Insights and Potential Clinical Utility.Cancers · 2025Review
- Insights into the role of collided ribosomes during the activation of the integrated stress response.Biochemical Society transactions · 2025Review
- eEF2K regulates pain through translational control of BDNF.Molecular cell · 2025Article
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9 authors.
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Abstract
18S nonfunctional rRNA decay (NRD) detects and eliminates translationally nonfunctional 18S rRNA. Although this process is critical for ribosome quality control, the mechanisms underlying nonfunctional 18S rRNA turnover remain elusive, particularly in mammals. Here, we show that mammalian 18S NRD initiates through the integrated stress response (ISR) via GCN2. Nonfunctional 18S rRNA induces translational arrest at start sites. Biochemical analyses demonstrate that ISR activation limits translation initiation and attenuates collisions between scanning 43S preinitiation complexes and stalled nonfunctional ribosomes. The ISR promotes 18S NRD and 40S ribosomal protein turnover by RNF10-mediated ubiquitination. Ultimately, RIOK3 binds the resulting ubiquitinated 40S subunits and facilitates 18S rRNA decay. Overall, mammalian 18S NRD acts through GCN2, followed by ubiquitin-dependent 18S rRNA degradation involving the ubiquitin E3 ligase RNF10 and the atypical protein kinase RIOK3. These findings establish a dynamic feedback mechanism by which the GCN2-RNF10-RIOK3 axis surveils ribosome functionality at the translation initiation step.
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