Evidence map›Paper›PMID 31165876›Full record

ArticleNucleic acids research2019

mRNA levels can be reduced by antisense oligonucleotides via no-go decay pathway.

Xue-Hai Liang, Joshua G Nichols, Chih-Wei Hsu, Timothy A Vickers, Stanley T Crooke

Open access · goldAbstract read
In one paragraph

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 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
1.9field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

41 citing papers in PubMed, 56 citations in OpenAlex.

  1. Article
  2. Review
  3. The Versatile Applications of Antisense Oligonucleotides in Modern Medicine.International journal of molecular sciences · 2026
    Review
  4. Review
  5. Advances in antisense oligonucleotide treatment for cancer.Japanese journal of clinical oncology · 2026
    Review
  6. Article
  7. Antisense Oligonucleotide Therapeutics Targeting Age-Related Diseases.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026
    Review
  8. Genetic therapies for neurological diseases.Pharmacological reviews · 2026
    Review
  9. Antisense oligonucleotide-mediated upregulation ofMolecular therapy. Nucleic acids · 2025
    Article
  10. Review
  11. Review
  12. Structural Characterization ofInternational journal of molecular sciences · 2025
    Article
  13. Review
  14. Review
  15. Review
  16. Review
  17. Review
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Xue-Hai LiangDepartment of Core Antisense Research, Ionis Pharmaceutics, Inc., 2855 Gazelle Court, Carlsbad, CA 92010, USA.
Joshua G NicholsDepartment of Core Antisense Research, Ionis Pharmaceutics, Inc., 2855 Gazelle Court, Carlsbad, CA 92010, USA.
Chih-Wei HsuDepartment of Core Antisense Research, Ionis Pharmaceutics, Inc., 2855 Gazelle Court, Carlsbad, CA 92010, USA.
Timothy A VickersDepartment of Core Antisense Research, Ionis Pharmaceutics, Inc., 2855 Gazelle Court, Carlsbad, CA 92010, USA.
Stanley T CrookeDepartment of Core Antisense Research, Ionis Pharmaceutics, Inc., 2855 Gazelle Court, Carlsbad, CA 92010, USA.
Ionis Pharmaceuticals (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Antisense technology can reduce gene expression via the RNase H1 or RISC pathways and can increase gene expression through modulation of splicing or translation. Here, we demonstrate that antisense oligonucleotides (ASOs) can reduce mRNA levels by acting through the no-go decay pathway. Phosphorothioate ASOs fully modified with 2'-O-methoxyethyl decreased mRNA levels when targeted to coding regions of mRNAs in a translation-dependent, RNase H1-independent manner. The ASOs that activated this decay pathway hybridized near the 3' end of the coding regions. Although some ASOs induced nonsense-mediated decay, others reduced mRNA levels through the no-go decay pathway, since depletion of PELO/HBS1L, proteins required for no-go decay pathway activity, decreased the activities of these ASOs. ASO length and chemical modification influenced the efficacy of these reagents. This non-gapmer ASO-induced mRNA reduction was observed for different transcripts and in different cell lines. Thus, our study identifies a new mechanism by which mRNAs can be degraded using ASOs, adding a new antisense approach to modulation of gene expression. It also helps explain why some fully modified ASOs cause RNA target to be reduced despite being unable to serve as substrates for RNase H1.

Indexed as

AnimalsCell LineCell Line, TumorEndonucleasesGTP-Binding ProteinsHot TemperatureMiceNuclear ProteinsNucleic Acid DenaturationNucleolinOligonucleotides, AntisensePhosphoproteinsPhosphorothioate OligonucleotidesProtein BiosynthesisRNA-Binding ProteinsRNA InterferenceEndonucleasesGTP-Binding ProteinsHBS1L protein, humanLa protein, humanNuclear ProteinsNucleolinOligonucleotides, Antisensepelo protein, humanPhosphoproteinsPhosphorothioate OligonucleotidesRNA-Binding ProteinsRNA, MessengerRNA, Small Interfering

Identifiers

PMID31165876
PMCPMC6649848
OpenAlexW2963472015

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.