ArticlePLoS genetics2020
Pathological mechanism and antisense oligonucleotide-mediated rescue of a non-coding variant suppressing factor 9 RNA biogenesis leading to hemophilia B.
Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 7 papers.
What it found
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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.
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Who cites it
7 citing papers in PubMed, 9 citations in OpenAlex.
- Molecular mechanisms and therapeutic strategies for the recurrent F9 (c.520 + 13 A > G) variant in hemophilia B.Human genomics · 2026Article
- A nuclear RNA degradation code is recognized by PAXT for eukaryotic transcriptome surveillance.Molecular cell · 2025Article
- Decoding Non-coding Variants: Recent Approaches to Studying Their Role in Gene Regulation and Human Diseases.Frontiers in bioscience (Scholar edition) · 2024Review
- A transposable element prevents severe hemophilia B and provides insights into the evolution of new- and old world primates.PloS one · 2024Article
- Multicenter Study of Diagnostic Tool for Patients with Hemophilia: From Bedside to Comprehensive Investigations.The application of clinical genetics · 2023Article
- Splicing factor PRP-19 regulates mitochondrial stress response.Life metabolism · 2022Article
- Correction: Pathological mechanism and antisense oligonucleotide-mediated rescue of a non-coding variant suppressing factor 9 RNA biogenesis leading to hemophilia B.PLoS genetics · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Loss-of-function mutations in the human coagulation factor 9 (F9) gene lead to hemophilia B. Here, we dissected the consequences and the pathomechanism of a non-coding mutation (c.2545A>G) in the F9 3' untranslated region. Using wild type and mutant factor IX (FIX) minigenes we revealed that the mutation leads to reduced F9 mRNA and FIX protein levels and to lower coagulation activity of cell culture supernatants. The phenotype could not be compensated by increased transcription. The pathomechanism comprises the de novo creation of a binding site for the spliceosomal component U1snRNP, which is able to suppress the nearby F9 poly(A) site. This second, splicing-independent function of U1snRNP was discovered previously and blockade of U1snRNP restored mutant F9 mRNA expression. In addition, we explored the vice versa approach and masked the mutation by antisense oligonucleotides resulting in significantly increased F9 mRNA expression and coagulation activity. This treatment may transform the moderate/severe hemophilia B into a mild or subclinical form in the patients. This antisense based strategy is applicable to other mutations in untranslated regions creating deleterious binding sites for cellular proteins.
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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.