Evidence map›Paper›PMID 38514771›Full record

ArticleLeukemia2024

Impaired binding affinity of YTHDC1 with METTL3/METTL14 results in R-loop accumulation in myelodysplastic neoplasms with DDX41 mutation.

Won Chan Hwang, Kibeom Park, Silvia Park, Na Young Cheon, Ja Yil Lee, Taejoo Hwang, Semin Lee, Jong-Mi Lee, Min Kyung Ju, Joo Rak Lee and 5 more

Open access · hybridAbstract read
In one paragraph

Article in Leukemia, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
13.6field-weighted citation impact, top 1% 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

28 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
  2. Article
  3. Germline DDX41 mutations in myeloid neoplasms: a comprehensive review.The Korean journal of internal medicine · 2026
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. mActa pharmaceutica Sinica. B · 2025
    Review
  12. Dual roles of NScience China. Life sciences · 2025
    Article
  13. METTL16-dependent GPX4 mBMC cancer · 2025
    Article
  14. Article
  15. Review
  16. Review
  17. RNA mCell investigation · 2025
    Article
  18. Review
  19. Article
  20. Mechanisms underlining R-loop biology and implications for human disease.Frontiers in cell and developmental biology · 2025
    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

15 authors at 4 institutions in 2 countries.

Won Chan Hwang *Department of Biological Sciences, Ulsan National Institute of Science and Technology, Ulsan, Korea.ORCID 0000-0001-9069-4576
Kibeom Park *Department of Biological Sciences, Ulsan National Institute of Science and Technology, Ulsan, Korea.
Silvia Park *Department of Hematology, Seoul St. Mary's Hematology Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Na Young Cheon *Department of Biological Sciences, Ulsan National Institute of Science and Technology, Ulsan, Korea.ORCID 0000-0001-8592-5931
Ja Yil Lee *Department of Biological Sciences, Ulsan National Institute of Science and Technology, Ulsan, Korea.
Taejoo HwangDepartment of Biomedical Engineering, College of Information and Biotechnology, Ulsan National Institute of Science and Technology, Ulsan, Korea.
Semin LeeDepartment of Biomedical Engineering, College of Information and Biotechnology, Ulsan National Institute of Science and Technology, Ulsan, Korea.
Jong-Mi LeeCatholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Min Kyung JuDepartment of Biological Sciences, Ulsan National Institute of Science and Technology, Ulsan, Korea.
Joo Rak LeeDepartment of Biological Sciences, Ulsan National Institute of Science and Technology, Ulsan, Korea.
Yong-Rim KwonLeukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Woo-Lam JoCatholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Myungshin KimCatholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea. microkim@catholic.ac.kr.ORCID 0000-0001-8632-0168
Yoo-Jin KimDepartment of Hematology, Seoul St. Mary's Hematology Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea. yoojink@catholic.ac.kr.
Hongtae KimDepartment of Biological Sciences, Ulsan National Institute of Science and Technology, Ulsan, Korea. khtcat@unist.ac.kr.
Ulsan National Institute of Science and Technology · KRThe Catholic University of Korea Seoul St. Mary's Hospital · KRCatholic University of Korea · KRSt. Mary's Hospital · US

Funding

National Research Foundation of Korea (NRF) NRF-2021R1A2C1006913National Research Foundation of Korea (NRF) NRF-2021R1F1A1052400National Research Foundation of Korea (NRF) NRF-2021R1I1A1A01059572National Research Foundation of Korea (NRF) NRF-2022R1A2C2006746National Research Foundation of Korea (NRF) NRF-2022R1A4A1021318Samsung SSTF-BA1901-13
6 · The paper itself

Abstract

DEAD box helicase 41 (DDX41) mutations are the most prevalent predisposition to familial myelodysplastic syndrome (MDS). However, the precise roles of these variants in the pathogenesis of MDS have yet to be elucidated. Here, we discovered a novel mechanism by which DDX41 contributes to R-loop-induced DNA damage responses (DDR) in cooperation with the m6A-METTL complex (MAC) and YTHDC1 using DDX41 knockout (KO) and DDX41 knock-in (KI, R525H, Y259C) cell lines as well as primary samples from MDS patients. Compared to wild type (WT), DDX41 KO and KI led to increased levels of m6A RNA methylated R-loop. Interestingly, we found that DDX41 regulates m6A/R-loop levels by interacting with MAC components. Further, DDX41 promoted the recruitment of YTHDC1 to R-loops by promoting the binding between METTL3 and YTHDC1, which was dysregulated in DDX41-deficient cells, contributing to genomic instability. Collectively, we demonstrated that DDX41 plays a key role in the physiological control of R-loops in cooperation with MAC and YTHDC1. These findings provide novel insights into how defects in DDX41 influence MDS pathogenesis and suggest potential therapeutic targets for the treatment of MDS.

Indexed as

DEAD-box RNA HelicasesMethyltransferasesMutationMyelodysplastic SyndromesRNA Splicing FactorsDNA DamageHumansNerve Tissue ProteinsProtein BindingR-Loop StructuresDDX41 protein, humanDEAD-box RNA HelicasesMethyltransferasesMETTL14 protein, humanMETTL3 protein, humanNerve Tissue ProteinsRNA Splicing FactorsYTHDC1 protein, human

Identifiers

PMID38514771
PMCPMC11147762
OpenAlexW4393055938

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.