Evidence map›Paper›PMID 34329467›Full record

ArticleNucleic acids research2021

TDRD3 promotes DHX9 chromatin recruitment and R-loop resolution.

Wei Yuan, Qais Al-Hadid, Zhihao Wang, Lei Shen, Hyejin Cho, Xiwei Wu, Yanzhong Yang

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
4.5field-weighted citation impact, top 4% 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

47 citing papers in PubMed, 69 citations in OpenAlex.

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  8. Differential roles of type I topoisomerases in regulating HPV pathogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  17. Topoisomerase IIIβ protects from tumorigenesis and immune dysregulation.bioRxiv : the preprint server for biology · 2025
    Article
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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

7 authors at 1 institution in 1 country.

Wei YuanDepartment of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope National Cancer Center, Duarte, CA 91010, USA.
Qais Al-HadidDepartment of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope National Cancer Center, Duarte, CA 91010, USA.
Zhihao WangDepartment of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope National Cancer Center, Duarte, CA 91010, USA.
Lei ShenDepartment of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope National Cancer Center, Duarte, CA 91010, USA.
Hyejin ChoDepartment of Molecular and Cellular Biology, Beckman Research Institute, City of Hope National Cancer Center, Duarte, CA 91010, USA.
Xiwei WuDepartment of Molecular and Cellular Biology, Beckman Research Institute, City of Hope National Cancer Center, Duarte, CA 91010, USA.
Yanzhong YangDepartment of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope National Cancer Center, Duarte, CA 91010, USA.ORCID 0000-0002-1937-4526
City Of Hope National Medical Center · US

Funding

Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI STANLEY R. HAMILTON · 1985 to 2026
$86.3M
DNA Damage Response and Oncogenic SignalingT32CA186895 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI BINGHUI SHEN, Jeremy Michael Stark · 2016 to 2026
$2.1M
Regulation of N6-methyladenosine (m6A) deposition by arginine methylationR01GM133850 · NIGMS · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI YANG, YANZHONG · 2019 to 2023
$2.1M
NCI NIH HHS P30 CA033572NCI NIH HHS T32 CA186895NIGMS NIH HHS R01 GM133850
6 · The paper itself

Abstract

R-loops, which consist of a DNA/RNA hybrid and a displaced single-stranded DNA (ssDNA), are increasingly recognized as critical regulators of chromatin biology. R-loops are particularly enriched at gene promoters, where they play important roles in regulating gene expression. However, the molecular mechanisms that control promoter-associated R-loops remain unclear. The epigenetic 'reader' Tudor domain-containing protein 3 (TDRD3), which recognizes methylarginine marks on histones and on the C-terminal domain of RNA polymerase II, was previously shown to recruit DNA topoisomerase 3B (TOP3B) to relax negatively supercoiled DNA and prevent R-loop formation. Here, we further characterize the function of TDRD3 in R-loop metabolism and introduce the DExH-box helicase 9 (DHX9) as a novel interaction partner of the TDRD3/TOP3B complex. TDRD3 directly interacts with DHX9 via its Tudor domain. This interaction is important for recruiting DHX9 to target gene promoters, where it resolves R-loops in a helicase activity-dependent manner to facilitate gene expression. Additionally, TDRD3 also stimulates the helicase activity of DHX9. This stimulation relies on the OB-fold of TDRD3, which likely binds the ssDNA in the R-loop structure. Thus, DHX9 functions together with TOP3B to suppress promoter-associated R-loops. Collectively, these findings reveal new functions of TDRD3 and provide important mechanistic insights into the regulation of R-loop metabolism.

Indexed as

Promoter Regions, GeneticR-Loop StructuresChromatinDEAD-box RNA HelicasesDNA Topoisomerases, Type IHEK293 CellsHumansMCF-7 CellsNeoplasm ProteinsProtein Interaction Domains and MotifsProteinsTranscription, GeneticChromatinDEAD-box RNA HelicasesDHX9 protein, humanDNA Topoisomerases, Type INeoplasm ProteinsProteinsTdrd3 protein, humanTOP3B protein, human

Identifiers

PMID34329467
PMCPMC8421139
OpenAlexW3186499224

What OpenQuestion holds

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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.