ArticleNucleic acids research2016
RNA cleavage products generated by antisense oligonucleotides and siRNAs are processed by the RNA surveillance machinery.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 67 citations in OpenAlex.
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- Integrating transcriptomics and proteomics to assess antisense oligonucleotide safety and efficacy: a time-resolved approach.NAR molecular medicine · 2026Article
- Gene Targeted Therapies for Neurodegenerative Disorders: Strategies and Implications in ALS and SMA.Genes · 2026Review
- RNA-Based Therapies for Inherited Metabolic Disorders.Journal of inherited metabolic disease · 2026Review
- Genetic therapies for neurological diseases.Pharmacological reviews · 2026Review
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- Splice-Modulating Antisense Oligonucleotides as Therapeutics for Inherited Metabolic Diseases.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
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- Lipid nanovehicles overcome barriers to systemic RNA delivery: Lipid components, fabrication methods, and rational design.Acta pharmaceutica Sinica. B · 2024Review
- Precise transcript targeting by CRISPR-Csm complexes.Nature biotechnology · 2023Article
- CD95/Fas ligand mRNA is toxic to cells through more than one mechanism.Molecular biomedicine · 2023Article
- The Small RNA Landscape in NSCLC: Current Therapeutic Applications and Progresses.International journal of molecular sciences · 2023Review
- Gene targeting as a therapeutic avenue in diseases mediated by the complement alternative pathway.Immunological reviews · 2023Review
- Antisense technology: an overview and prospectus.Nature reviews. Drug discovery · 2021Review
- Short DNA/RNA heteroduplex oligonucleotide interacting proteins are key regulators of target gene silencing.Nucleic acids research · 2021Article
- The Challenges and Strategies of Antisense Oligonucleotide Drug Delivery.Biomedicines · 2021Review
- Comparative parallel analysis of RNA ends identifies mRNA substrates of a tRNA splicing endonuclease-initiated mRNA decay pathway.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
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
DNA-based antisense oligonucleotides (ASOs) elicit cleavage of the targeted RNA by the endoribonuclease RNase H1, whereas siRNAs mediate cleavage through the RNAi pathway. To determine the fates of the cleaved RNA in cells, we lowered the levels of the factors involved in RNA surveillance prior to treating cells with ASOs or siRNA and analyzed cleavage products by RACE. The cytoplasmic 5' to 3' exoribonuclease XRN1 was responsible for the degradation of the downstream cleavage products generated by ASOs or siRNA targeting mRNAs. In contrast, downstream cleavage products generated by ASOs targeting nuclear long non-coding RNA Malat 1 and pre-mRNA were degraded by nuclear XRN2. The downstream cleavage products did not appear to be degraded in the 3' to 5' direction as the majority of these products contained intact poly(A) tails and were bound by the poly(A) binding protein. The upstream cleavage products of Malat1 were degraded in the 3' to 5' direction by the exosome complex containing the nuclear exoribonuclease Dis3. The exosome complex containing Dis3 or cytoplasmic Dis3L1 degraded mRNA upstream cleavage products, which were not bound by the 5'-cap binding complex and, consequently, were susceptible to degradation in the 5' to 3' direction by the XRN exoribonucleases.
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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.