ArticleNature2016
Failure of RQC machinery causes protein aggregation and proteotoxic stress.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
142 citing papers in PubMed.
- Regulation of cellular proteostasis via mitochondrial protein import.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- TOR-NOT4 signalling couples translation to co-translational quality control in plants.Nature communications · 2026Article
- The coordinated action of UFMylation and the RQC pathways clears arrested polypeptides at the ER.The EMBO journal · 2026Article
- Ribosome Molecular Aging Shapes Translation Dynamics.bioRxiv : the preprint server for biology · 2026Article
- Unveiling ribosomal dysfunction and impaired signaling pathways in the cortical region of 5xFAD mice.Acta neuropathologica communications · 2026Article
- Quality control and signaling pathways at stalled ribosomes.Experimental & molecular medicine · 2026Review
- Article
- Chronic stress antagonizes formation of stress granules.iScience · 2026Article
- Ribosome-associated quality control of aberrant protein production during amino acid limitation.bioRxiv : the preprint server for biology · 2026Article
- Mitochondrial Protein Carboxyl-Terminal Alanine-Threonine Tailing Promotes Human Glioblastoma Growth by Regulating Mitochondrial Function.bioRxiv : the preprint server for biology · 2026Article
- Mechanical forces regulate the composition and fate of stalled nascent chains.Molecular cell · 2026Article
- Regulation via compartmentation: adaptive localization of the proteasome under stress.Biochemical Society transactions · 2025Review
- Chromosome duplication causes premature aging via defects in ribosome quality control.PLoS biology · 2025Article
- Defective Ribosome Recycling: A Bridge Between Translation Fidelity, Organelle Dysfunction, and Diseases: Exploring How Flawed Ribosome Recycling Factors Impact Ribosome Metabolism and Organelle Homeostasis, Leading to Human Diseases.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Mechanism of nascent chain removal by the ribosome-associated quality control complex.Nature communications · 2025Article
- Reactivation of the tRNASer/tRNATyr gene cluster in Arabidopsis thaliana root tips.The Plant cell · 2025Article
- Proteostasis and Its Role in Disease Development.Cell biochemistry and biophysics · 2025Review
- UFMylation orchestrates spatiotemporal coordination of RQC at the ER.Science advances · 2025Article
- Proteostasis and metabolic dysfunction characterize a subset of storage-induced senescent erythrocytes targeted for posttransfusion clearance.The Journal of clinical investigation · 2025Article
- Dysregulated ribosome quality control in human diseases.The FEBS journal · 2025Review
82 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Translation of messenger RNAs lacking a stop codon results in the addition of a carboxy-terminal poly-lysine tract to the nascent polypeptide, causing ribosome stalling. Non-stop proteins and other stalled nascent chains are recognized by the ribosome quality control (RQC) machinery and targeted for proteasomal degradation. Failure of this process leads to neurodegeneration by unknown mechanisms. Here we show that deletion of the E3 ubiquitin ligase Ltn1p in yeast, a key RQC component, causes stalled proteins to form detergent-resistant aggregates and inclusions. Aggregation is dependent on a C-terminal alanine/threonine tail that is added to stalled polypeptides by the RQC component, Rqc2p. Formation of inclusions additionally requires the poly-lysine tract present in non-stop proteins. The aggregates sequester multiple cytosolic chaperones and thereby interfere with general protein quality control pathways. These findings can explain the proteotoxicity of ribosome-stalled polypeptides and demonstrate the essential role of the RQC in maintaining proteostasis.
Indexed as
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.