ArticleNucleic acids research2014
A novel phosphorylation-independent interaction between SMG6 and UPF1 is essential for human NMD.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 99 citations in OpenAlex.
- TDP-43 promotes allergen-induced inflammation and influenza A virus replication in airway epithelium.Nature communications · 2026Article
- NMD takes two PIN domains to tango.RNA (New York, N.Y.) · 2026Article
- SMG1:SMG8:SMG9-complex integrity supports efficient execution of nonsense-mediated mRNA decay.Nucleic acids research · 2026Article
- Composite SMG5-SMG6 PIN domain formation is essential for NMD.Nature communications · 2026Article
- Nonsense-Mediated mRNA Decay in Human Health and Diseases: Current Understanding, Regulatory Mechanisms and Future Perspectives.Molecular biotechnology · 2025Review
- Biological roles of nonsense-mediated RNA decay: insights from the nervous system.Current opinion in genetics & development · 2025Review
- Up-Frameshift Factors from Phytopathogenic Fungi Play a Crucial Role in Nonsense-Mediated mRNA Decay.Journal of fungi (Basel, Switzerland) · 2025Article
- Messenger RNA Surveillance: Current Understanding, Regulatory Mechanisms, and Future Implications.Molecular biotechnology · 2025Review
- Modulation of UPF1 catalytic activity upon interaction of SARS-CoV-2 Nucleocapsid protein with factors involved in nonsense mediated-mRNA decay.Nucleic acids research · 2024Article
- A Comparative Overview of the Role of Human Ribonucleases in Nonsense-Mediated mRNA Decay.Genes · 2024Article
- Structure of the Nmd4-Upf1 complex supports conservation of the nonsense-mediated mRNA decay pathway between yeast and humans.PLoS biology · 2024Article
- UPF1 helicase orchestrates mutually exclusive interactions with the SMG6 endonuclease and UPF2.Nucleic acids research · 2024Article
- UPF1 ATPase autoinhibition and activation modulate RNA binding kinetics and NMD efficiency.Nucleic acids research · 2024Article
- Translational enhancement of target endogenous mRNA in mammalian cells using programmable RNA-binding pentatricopeptide repeat proteins.Scientific reports · 2024Article
- UPF1 ATPase autoinhibition and activation modulate RNA binding kinetics and NMD efficiency.bioRxiv : the preprint server for biology · 2023Article
- 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
- Modulation of RNA-binding properties of the RNA helicase UPF1 by its activator UPF2.RNA (New York, N.Y.) · 2023Article
- UPF1 mutants with intact ATPase but deficient helicase activities promote efficient nonsense-mediated mRNA decay.Nucleic acids research · 2022Article
- Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Eukaryotic mRNAs with premature translation-termination codons (PTCs) are recognized and eliminated by nonsense-mediated mRNA decay (NMD). NMD substrates can be degraded by different routes that all require phosphorylated UPF1 (P-UPF1) as a starting point. The endonuclease SMG6, which cleaves mRNA near the PTC, is one of the three known NMD factors thought to be recruited to nonsense mRNAs via an interaction with P-UPF1, leading to eventual mRNA degradation. By artificial tethering of SMG6 and mutants thereof to a reporter mRNA combined with knockdowns of various NMD factors, we demonstrate that besides its endonucleolytic activity, SMG6 also requires UPF1 and SMG1 to reduce reporter mRNA levels. Using in vivo and in vitro approaches, we further document that SMG6 and the unique stalk region of the UPF1 helicase domain, along with a contribution from the SQ domain, form a novel interaction and we also show that this region of the UPF1 helicase domain is critical for SMG6 function and NMD. Our results show that this interaction is required for NMD and for the capability of tethered SMG6 to degrade its bound RNA, suggesting that it contributes to the intricate regulation of UPF1 and SMG6 enzymatic activities.
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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.