ArticleNucleic acids research2018
Translation can affect the antisense activity of RNase H1-dependent oligonucleotides targeting mRNAs.
Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 21 citations in OpenAlex.
- Transcription factor targeting strategies in cancer: mechanisms, challenges and cutting-edge progress.Acta pharmacologica Sinica · 2026Review
- Nucleic Acid Therapeutics for "Undruggable" Cancer Targets: Mechanisms, Challenges, and Prospects.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Advancements in RNA-based therapies from bench to bedside.npj drug discovery · 2026Review
- The efficacy of oligonucleotide-based gene therapeutics in gene silencing.Theranostics · 2026Review
- Structural Characterization ofInternational journal of molecular sciences · 2025Article
- Frameworks for transformational breakthroughs in RNA-based medicines.Nature reviews. Drug discovery · 2024Review
- Sequence-Specific Gene Silencing of acrA in the Multi-drug Efflux System AcrAB Induces Sensitivity in Drug-Resistant Klebsiella pneumoniae.Molecular biotechnology · 2023Article
- NAT10 and DDX21 Proteins Interact with RNase H1 and Affect the Performance of Phosphorothioate Oligonucleotides.Nucleic acid therapeutics · 2022Article
- Perinuclear positioning of endosomes can affect PS-ASO activities.Nucleic acids research · 2021Article
- Antisense technology: an overview and prospectus.Nature reviews. Drug discovery · 2021Review
- Pharmacokinetics and Proceedings in Clinical Application of Nucleic Acid Therapeutics.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- Some ASOs that bind in the coding region of mRNAs and induce RNase H1 cleavage can cause increases in the pre-mRNAs that may blunt total activity.Nucleic acids research · 2020Article
- Targeting Repeated Regions Unique to a Gene Is an Effective Strategy for Discovering Potent and Efficacious Antisense Oligonucleotides.Molecular therapy. Nucleic acids · 2020Article
- mRNA levels can be reduced by antisense oligonucleotides via no-go decay pathway.Nucleic acids research · 2019Article
- Differential uptake, kinetics and mechanisms of intracellular trafficking of next-generation antisense oligonucleotides across human cancer cell lines.Nucleic acids research · 2019Article
- COPII vesicles can affect the activity of antisense oligonucleotides by facilitating the release of oligonucleotides from endocytic pathways.Nucleic acids research · 2018Article
- Article
- Antisense technology: A review.The Journal of biological chemistryReview
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RNase H1-dependent antisense oligonucleotides (ASOs) can degrade complementary RNAs in both the nucleus and the cytoplasm. Since cytoplasmic mRNAs are actively engaged in translation, ASO activity may thus be affected by translating ribosomes that scan the mRNAs. Here we show that mRNAs associated with ribosomes can be cleaved using ASOs and that translation can alter ASO activity. Translation inhibition tends to increase ASO activity when targeting the coding regions of efficiently translated mRNAs, but not nuclear non-coding RNAs or less efficiently translated mRNAs. Increasing the level of RNase H1 protein eliminated the enhancing effects of translation inhibition on ASO activity, suggesting that RNase H1 recruitment to ASO/mRNA heteroduplexes is a rate limiting step and that translating ribosomes can inhibit RNase H1 recruitment. Consistently, ASO activity was not increased by translation inhibition when targeting the 3' UTRs, independent of the translation efficiency of the mRNAs. Contrarily, the activity of 3' UTR-targeting ASOs tended to be reduced upon translation inhibition, likely due to decreased accessibility. These results indicate that ASO activity can be affected by the translation process, and the findings also provide important information toward helping better ASO drug design.
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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.