ArticleMolecular biology of the cell2021
Selective destabilization of polypeptides synthesized from NMD-targeted transcripts.
Article in Molecular biology of the cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- RiboScreenBiomedicines · 2026Review
- Systematic analysis of nonsense variants uncovers peptide release rate as a novel modifier of nonsense-mediated mRNA decay.Cell genomics · 2025Article
- UPF1 helicase orchestrates mutually exclusive interactions with the SMG6 endonuclease and UPF2.Nucleic acids research · 2024Article
- Pervasive translation of Xrn1-sensitive unstable long noncoding RNAs in yeast.RNA (New York, N.Y.) · 2024Article
- A system of reporters for comparative investigation of EJC-independent and EJC-enhanced nonsense-mediated mRNA decay.Nucleic acids research · 2024Article
- Readthrough-induced misincorporated amino acid ratios guide mutant-specific therapeutic approaches for two CFTR nonsense mutations.Frontiers in pharmacology · 2024Article
- Game of Omes: ribosome profiling expands the MHC-I immunopeptidome.Current opinion in immunology · 2023Review
- Coupled protein quality control during nonsense-mediated mRNA decay.Journal of cell science · 2023Article
- Nonsense-Mediated mRNA Decay Factor Functions in Human Health and Disease.Biomedicines · 2023Review
- ATP13A1 prevents ERAD of folding-competent mislocalized and misoriented proteins.Molecular cell · 2022Article
- No-nonsense: insights into the functional interplay of nonsense-mediated mRNA decay factors.The Biochemical journal · 2022Review
- Nonsense-mediated mRNA decay uses complementary mechanisms to suppress mRNA and protein accumulation.Life science alliance · 2022Article
- Ending a bad start: Triggers and mechanisms of co-translational protein degradation.Frontiers in molecular biosciences · 2022Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The translation of mRNAs that contain a premature termination codon (PTC) generates truncated proteins that may have toxic dominant negative effects. Nonsense-mediated decay (NMD) is an mRNA surveillance pathway that degrades PTC-containing mRNAs to limit the production of truncated proteins. NMD activation requires a ribosome terminating translation at a PTC, but what happens to the polypeptides synthesized during the translation cycle needed to activate NMD is incompletely understood. Here, by establishing reporter systems that encode the same polypeptide sequence before a normal termination codon or PTC, we show that termination of protein synthesis at a PTC is sufficient to selectively destabilize polypeptides in mammalian cells. Proteasome inhibition specifically rescues the levels of nascent polypeptides produced from PTC-containing mRNAs within an hour, but also disrupts mRNA homeostasis within a few hours. PTC-terminated polypeptide destabilization is also alleviated by depleting the central NMD factor UPF1 or SMG1, the kinase that phosphorylates UPF1 to activate NMD, but not by inhibiting SMG1 kinase activity. Our results suggest that polypeptide degradation is linked to PTC recognition in mammalian cells and clarify a framework to investigate these mechanisms.
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Registered trials
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