Evidence map›Paper›PMID 35639772›Full record

ArticleNucleic acids research2022

HNRNPH1 destabilizes the G-quadruplex structures formed by G-rich RNA sequences that regulate the alternative splicing of an oncogenic fusion transcript.

Tam Vo, Tayvia Brownmiller, Katherine Hall, Tamara L Jones, Sulbha Choudhari, Ioannis Grammatikakis, Katelyn R Ludwig, Natasha J Caplen

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
3.1field-weighted citation impact, top 7% 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

32 citing papers in PubMed, 40 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
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  5. Review
  6. Microprotein Regulates G-quadruplex Driven RNA Aggregation.bioRxiv : the preprint server for biology · 2026
    Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. HNRNPH1-mediated splicing events regulatebioRxiv : the preprint server for biology · 2025
    Article
  13. Article
  14. Review
  15. Contributions of Folded and Disordered Domains to RNA Binding by HNRNPR.bioRxiv : the preprint server for biology · 2025
    Article
  16. Article
  17. Article
  18. Expanding the Functions of KHSRP Protein: Insights into DNA G-Quadruplex Binding.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    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

8 authors at 2 institutions in 1 country.

Tam VoFunctional Genetics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0002-0795-5163
Tayvia BrownmillerFunctional Genetics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Katherine HallFunctional Genetics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Tamara L JonesFunctional Genetics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Sulbha ChoudhariCCR-SF Bioinformatics Group, Biomedical Informatics and Data Science Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA.
Ioannis GrammatikakisRegulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Katelyn R LudwigFunctional Genetics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Natasha J CaplenFunctional Genetics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0002-0001-9460
National Institutes of Health · USFrederick National Laboratory for Cancer Research · US

Funding

Discovery of genes required for expression or activity of fusion oncogenesZIABC011704 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI CAPLEN, NATASHA · 2016 to 2025
$15.8M
Intramural NIH HHS ZIA BC011704
6 · The paper itself

Abstract

In the presence of physiological monovalent cations, thousands of RNA G-rich sequences can form parallel G-quadruplexes (G4s) unless RNA-binding proteins inhibit, destabilize, or resolve the formation of such secondary RNA structures. Here, we have used a disease-relevant model system to investigate the biophysical properties of the RNA-binding protein HNRNPH1's interaction with G-rich sequences. We demonstrate the importance of two EWSR1-exon 8 G-rich regions in mediating the exclusion of this exon from the oncogenic EWS-FLI1 transcripts expressed in a subset of Ewing sarcomas, using complementary analysis of tumor data, long-read sequencing, and minigene studies. We determined that HNRNPH1 binds the EWSR1-exon 8 G-rich sequences with low nM affinities irrespective of whether in a non-G4 or G4 state but exhibits different kinetics depending on RNA structure. Specifically, HNRNPH1 associates and dissociates from G4-folded RNA faster than the identical sequences in a non-G4 state. Importantly, we demonstrate using gel shift and spectroscopic assays that HNRNPH1, particularly the qRRM1-qRRM2 domains, destabilizes the G4s formed by the EWSR1-exon 8 G-rich sequences in a non-catalytic fashion. Our results indicate that HNRNPH1's binding of G-rich sequences favors the accumulation of RNA in a non-G4 state and that this contributes to its regulation of RNA processing.

Indexed as

G-QuadruplexesAlternative SplicingBase SequenceOncogenesRNARNA-Binding ProteinsRNARNA-Binding Proteins

Identifiers

PMID35639772
PMCPMC9226515
OpenAlexW4282927027

What OpenQuestion holds

Textmetadata
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.