ArticleNucleic acids research2022
UPF1 mutants with intact ATPase but deficient helicase activities promote efficient nonsense-mediated mRNA decay.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- An information theory approach to quantifying the sequence-dependent response of nucleic acid motors with applications to nanopore DNA sequencing.Nature communications · 2026Article
- Mechanistic insights into recruitment and regulation of the RNA helicase UPF1 in replication-dependent histone mRNA decay.Nature communications · 2026Article
- UPF1 shuttles between nucleus and cytoplasm independently of its RNA-binding and ATPase activities.RNA (New York, N.Y.) · 2025Article
- Synergistic Methods to Investigate Eukaryotic Translation and Its Quality Control.Journal of molecular biology · 2025Review
- Dynamic RNA binding and unfolding by nonsense-mediated mRNA decay factor UPF2.RNA (New York, N.Y.) · 2025Article
- The SARS-CoV-2 nucleocapsid protein interferes with the full enzymatic activation of UPF1 and its interaction with UPF2.Nucleic acids research · 2025Article
- 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
- UPF1 ATPase autoinhibition and activation modulate RNA binding kinetics and NMD efficiency.Nucleic acids research · 2024Article
- UPF1 ATPase autoinhibition and activation modulate RNA binding kinetics and NMD efficiency.bioRxiv : the preprint server for biology · 2023Article
- A new twist on PIFE: photoisomerisation-related fluorescence enhancement.Methods and applications in fluorescence · 2023Review
- Translation-coupled mRNA quality control mechanisms.The EMBO journal · 2023Review
- Article
- Two Single Nucleotide Deletions in theInternational journal of molecular sciences · 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
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The conserved RNA helicase UPF1 coordinates nonsense-mediated mRNA decay (NMD) by engaging with mRNAs, RNA decay machinery and the terminating ribosome. UPF1 ATPase activity is implicated in mRNA target discrimination and completion of decay, but the mechanisms through which UPF1 enzymatic activities such as helicase, translocase, RNP remodeling, and ATPase-stimulated dissociation influence NMD remain poorly defined. Using high-throughput biochemical assays to quantify UPF1 enzymatic activities, we show that UPF1 is only moderately processive (<200 nt) in physiological contexts and undergoes ATPase-stimulated dissociation from RNA. We combine an in silico screen with these assays to identify and characterize known and novel UPF1 mutants with altered helicase, ATPase, and RNA binding properties. We find that UPF1 mutants with substantially impaired processivity (E797R, G619K/A546H), faster (G619K) or slower (K547P, E797R, G619K/A546H) unwinding rates, and/or reduced mechanochemical coupling (i.e. the ability to harness ATP hydrolysis for work; K547P, R549S, G619K, G619K/A546H) can still support efficient NMD of well-characterized targets in human cells. These data are consistent with a central role for UPF1 ATPase activity in driving cycles of RNA binding and dissociation to ensure accurate NMD target selection.
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Registered trials
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