Evidence map›Paper›PMID 38589367›Full record

ArticleNature communications2024

Accelerated DNA replication fork speed due to loss of R-loops in myelodysplastic syndromes with SF3B1 mutation.

David Rombaut, Carine Lefèvre, Tony Rached, Sabrina Bondu, Anne Letessier, Raphael M Mangione, Batoul Farhat, Auriane Lesieur-Pasquier, Daisy Castillo-Guzman, Ismael Boussaid and 30 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
6.8field-weighted citation impact, top 3% 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

11 citing papers in PubMed, 15 citations in OpenAlex.

  1. RNA splicing in health and disease.Molecular biomedicine · 2026
    Review
  2. Splicing-driven post-translational dysregulation: a new frontier for precision cancer medicine and immunotherapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  3. Article
  4. Article
  5. The relevance of RNA-DNA interactions as regulators of physiological functions.Pflugers Archiv : European journal of physiology · 2025
    Review
  6. Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Review
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

40 authors at 8 institutions in 2 countries.

David Rombaut *Université Paris Cité, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut Cochin, Paris, France.ORCID http://orcid.org/0000-0001-8910-0945
Carine Lefèvre *Université Paris Cité, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut Cochin, Paris, France.ORCID http://orcid.org/0000-0003-3590-2445
Tony RachedUniversité Paris Cité, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut Cochin, Paris, France.ORCID http://orcid.org/0009-0001-1347-7479
Sabrina BonduUniversité Paris Cité, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut Cochin, Paris, France.
Anne LetessierUniversité Paris Cité, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut Cochin, Paris, France.ORCID http://orcid.org/0000-0002-1894-4072
Raphael M MangioneUniversité Paris Cité, CNRS, Institut Jacques Monod, Paris, France.ORCID http://orcid.org/0000-0001-6180-1926
Batoul FarhatUniversité Paris Cité, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut Cochin, Paris, France.ORCID http://orcid.org/0000-0001-9462-8840
Auriane Lesieur-PasquierUniversité Paris Cité, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut Cochin, Paris, France.
Daisy Castillo-GuzmanDepartment of Molecular and Cellular Biology and Genome Center, University of California, Davis, CA, USA.
Ismael BoussaidUniversité Paris Cité, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut Cochin, Paris, France.ORCID http://orcid.org/0000-0002-1839-8411
Chloé FriedrichUniversité Paris Cité, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut Cochin, Paris, France.ORCID http://orcid.org/0000-0002-8640-9776
Aurore TourvilleUniversité Paris Cité, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut Cochin, Paris, France.ORCID http://orcid.org/0009-0008-2755-8369
Magali De CarvalhoUniversité Paris Cité, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut Cochin, Paris, France.
Françoise LevavasseurUniversité Paris Cité, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut Cochin, Paris, France.ORCID http://orcid.org/0000-0001-6775-4542
Marjorie LeducUniversité Paris Cité, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut Cochin, Paris, France.ORCID http://orcid.org/0000-0002-4049-3976
Morgane Le GallUniversité Paris Cité, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut Cochin, Paris, France.ORCID http://orcid.org/0000-0002-4935-7065
Sarah BattaultUniversité Paris Cité, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut Cochin, Paris, France.
Marie TempleAssistance Publique-Hôpitaux de Paris.Centre-Université Paris Cité, Hôpital Cochin, Laboratory of Hematology, Paris, France.ORCID http://orcid.org/0000-0002-5247-8976
Alexandre HouyInstitut Curie, PSL Research University, Sorbonne University, INSERM U830, DNA repair and uveal melanoma, Equipe labellisée par la Ligue Nationale contre le Cancer, Paris, France.ORCID http://orcid.org/0000-0001-6267-2353
Didier BouscaryUniversité Paris Cité, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut Cochin, Paris, France.
Lise WillemsUniversité Paris Cité, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut Cochin, Paris, France.
Sophie ParkDepartment of Hematology, Centre Hospitalier Universitaire, Université de Grenoble Alpes, Grenoble, France.ORCID http://orcid.org/0000-0003-0514-5789
Sophie RaynaudLaboratory of Hematology, Université Côte d'Azur, Centre Hospitalier Universitaire, Nice, France.
Thomas CluzeauClinical Department of Hematology, Université Côte d'Azur, Centre Hospitalier Universitaire, Nice, France.ORCID http://orcid.org/0000-0002-6745-1127
Emmanuelle ClappierAssistance Publique-Hôpitaux de Paris.Nord-Université Paris Cité, Saint-Louis Hospital, Laboratory of Hematology, Paris, France.
Pierre FenauxAssistance Publique-Hôpitaux de Paris.Nord-Université Paris Cité, Saint-Louis Hospital, Service Hématologie Séniors, Paris, France.
Lionel AdèsAssistance Publique-Hôpitaux de Paris.Nord-Université Paris Cité, Saint-Louis Hospital, Service Hématologie Séniors, Paris, France.ORCID http://orcid.org/0000-0002-9020-8766
Raphael MargueronInstitut Curie, Paris Sciences Lettres Research University, Sorbonne University, INSERM U934, UMR3215, Paris, France.ORCID http://orcid.org/0000-0002-9093-7977
Michel WassefInstitut Curie, Paris Sciences Lettres Research University, Sorbonne University, INSERM U934, UMR3215, Paris, France.
Samar AlsafadiInstitut Curie, PSL Research University, Sorbonne University, INSERM U830, DNA repair and uveal melanoma, Equipe labellisée par la Ligue Nationale contre le Cancer, Paris, France.ORCID http://orcid.org/0000-0002-0060-1346
Nicolas ChapuisUniversité Paris Cité, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut Cochin, Paris, France.ORCID http://orcid.org/0000-0003-0601-3948
Olivier KosmiderUniversité Paris Cité, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut Cochin, Paris, France.ORCID http://orcid.org/0000-0002-6021-4057
Eric SolaryInstitut Gustave Roussy, INSERM 1287, Université Paris Saclay, Villejuif, France.ORCID http://orcid.org/0000-0002-8629-1341
Angelos ConstantinouInstitut de Génétique Humaine, Centre National de la Recherche Scientifique, Université de Montpellier, Montpellier, France.ORCID http://orcid.org/0000-0002-2994-8140
Marc-Henri SternInstitut Curie, PSL Research University, Sorbonne University, INSERM U830, DNA repair and uveal melanoma, Equipe labellisée par la Ligue Nationale contre le Cancer, Paris, France.ORCID http://orcid.org/0000-0002-8100-2272
Nathalie DroinInstitut Gustave Roussy, INSERM 1287, Université Paris Saclay, Villejuif, France.ORCID http://orcid.org/0000-0002-6099-5324
Benoit PalancadeUniversité Paris Cité, CNRS, Institut Jacques Monod, Paris, France.ORCID http://orcid.org/0000-0002-3894-9735
Benoit MiottoUniversité Paris Cité, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut Cochin, Paris, France.ORCID http://orcid.org/0000-0003-2857-2126
Frédéric ChédinDepartment of Molecular and Cellular Biology and Genome Center, University of California, Davis, CA, USA.ORCID http://orcid.org/0000-0002-1306-5335
Michaela FontenayUniversité Paris Cité, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut Cochin, Paris, France. michaela.fontenay@inserm.fr.ORCID http://orcid.org/0000-0002-5492-6349
Université Paris Cité · FRInserm · FRCentre National de la Recherche Scientifique · FRUniversité Côte d'Azur · FRUniversity of California, Davis · USCentre Hospitalier Universitaire de Grenoble · FRDélégation Paris 5 · FRUniversité de Montpellier · FR

Funding

UC Davis MCB T32 Administrative Supplement to Recognize Excellence in Diversity, Equity, Inclusion, and Accessibility (DEIA) MentorshipT32GM007377 · NIGMS · UNIVERSITY OF CALIFORNIA DAVIS · PI CHEDIN, FREDERIC LOUIS · 1985 to 2023
$9.9M
Understanding the mechanisms underlying R-loop biogenesis and resolution in mammals.R35GM139549 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Frederic Louis Chedin · 2021 to 2026
$4.4M
Uncovering novel roles for splicing factor SF3B1 in transcription dynamics, R-loop metabolism, and chromatin structureF31GM136143 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI CASTILLO GUZMAN, DAISY · 2020 to 2021
$76k
NIGMS NIH HHS F31 GM136143NIGMS NIH HHS R35 GM139549NIGMS NIH HHS T32 GM007377
6 · The paper itself

Abstract

Myelodysplastic syndromes (MDS) with mutated SF3B1 gene present features including a favourable outcome distinct from MDS with mutations in other splicing factor genes SRSF2 or U2AF1. Molecular bases of these divergences are poorly understood. Here we find that SF3B1-mutated MDS show reduced R-loop formation predominating in gene bodies associated with intron retention reduction, not found in U2AF1- or SRSF2-mutated MDS. Compared to erythroblasts from SRSF2- or U2AF1-mutated patients, SF3B1-mutated erythroblasts exhibit augmented DNA synthesis, accelerated replication forks, and single-stranded DNA exposure upon differentiation. Importantly, histone deacetylase inhibition using vorinostat restores R-loop formation, slows down DNA replication forks and improves SF3B1-mutated erythroblast differentiation. In conclusion, loss of R-loops with associated DNA replication stress represents a hallmark of SF3B1-mutated MDS ineffective erythropoiesis, which could be used as a therapeutic target.

Indexed as

Myelodysplastic SyndromesR-Loop StructuresHumansMutationPhosphoproteinsRNA Splicing FactorsSerine-Arginine Splicing FactorsSplicing Factor U2AFTranscription FactorsPhosphoproteinsRNA Splicing FactorsSerine-Arginine Splicing FactorsSF3B1 protein, humanSplicing Factor U2AFTranscription Factors

Identifiers

PMID38589367
PMCPMC11001894
OpenAlexW4394577759

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.