ArticleNucleic acids research2019
Kinetic and subcellular analysis of PS-ASO/protein interactions with P54nrb and RNase H1.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- Chemically stabilized long antisense oligonucleotides perturb RNA exosome function.Nucleic acids research · 2026Article
- Acyclic artificial nucleic acid substitution expands the safe design space of gapmer ASOs by preventing P54nrb mislocalization.NAR molecular medicine · 2026Article
- Single-base 2'OMe-modified LNA and MOE gapmers selectively silenceMolecular therapy. Nucleic acids · 2026Article
- Synthesis and properties of l-RSC chemical biology · 2026Article
- Targeting "undruggable" cancer proteins: pharmacological challenges and emerging strategies.Translational cancer research · 2026Review
- Dysregulation of the DNA damage response by phosphorothioate antisense oligonucleotides.Nature communications · 2026Article
- Unraveling and controlling late-onset neurotoxicity of antisense oligonucleotides through strategic chemical modifications.Molecular therapy. Nucleic acids · 2025Article
- Article
- Antisense oligonucleotide therapies for monogenic disorders.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2025Article
- Chemical Modifications in Nucleic Acid Therapeutics.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Technologies for Targeted RNA Degradation and Induced RNA Decay.Chemical reviews · 2024Review
- Preventing acute neurotoxicity of CNS therapeutic oligonucleotides with the addition of CaMolecular therapy. Nucleic acids · 2024Article
- The bench to bedside journey of tricyclo-DNA antisense oligonucleotides for the treatment of Duchenne muscular dystrophy.RSC medicinal chemistry · 2024Review
- Preventing acute neurotoxicity of CNS therapeutic oligonucleotides with the addition of CabioRxiv : the preprint server for biology · 2024Article
- Profiling the interactome of oligonucleotide drugs by proximity biotinylation.Nature chemical biology · 2024Article
- Targeting RNA with synthetic oligonucleotides: Clinical success invites new challenges.Cell chemical biology · 2024Review
- Triazole-linked Nucleic Acids: Synthesis, Therapeutics and Synthetic Biology Applications.Current organic synthesis · 2024Review
- Drug Discovery Perspectives of Antisense Oligonucleotides.Biomolecules & therapeutics · 2023Review
- NONO enhances mRNA processing of super-enhancer-associated GATA2 and HAND2 genes in neuroblastoma.EMBO reports · 2023Article
- Nephrotoxicity of marketed antisense oligonucleotide drugs.Current opinion in toxicology · 2022Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The rapid RNase H1-dependent mislocalization of heterodimer proteins P54nrb and PSF to nucleoli is an early event in the pathway that explains the effects of most toxic phosphorothioate ASOs (PS-ASOs). Using a recently developed NanoLuciferace (NLuc)-based structural complementation reporter system which allows us to observe ASO/protein interactions in real time in live cells, we have determined that safe and toxic PS-ASOs associate with these proteins with kinetics and impact on subcellular localization that differ. Toxic PS-ASOs interact in a complex that includes RNase H1, P54nrb and PSF; but RNase H1/P54nrb complexes were observed in only the cells treated with toxic, but not safe PS-ASOs. In addition, experiments performed in vitro suggest that RNA is also a required component of the complex. The protein-protein interaction between P54nrb and RNase H1 requires the spacer region of RNAse H1, while the P54nrb core domains are required for association with RNase H1. In addition, we have determined that PS-ASOs bind P54nrb via RRM1 and RRM2, while they bind RNase H1 primarily via the hybrid binding domain, however catalytic domain interactions also contribute to overall affinity. These ASO-protein interactions are highly influenced by the chemistry of the PS-ASO binding environment, however little correlation between affinity for specific proteins and PS-ASO toxicity was observed.
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