ArticleThe EMBO journal2019
Arginine methylation of the DDX5 helicase RGG/RG motif by PRMT5 regulates resolution of RNA:DNA hybrids.
Article in The EMBO journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers.
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Who cites it
126 citing papers in PubMed, 184 citations in OpenAlex.
- Tools for Experimental and Computational Genome-Wide Analysis of the Function of DDX5 and DDX17 Helicases in RNA Processing.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Mechanisms of transcription termination across the coding and noncoding loci of the genome.Nature reviews. Molecular cell biology · 2026Review
- SIRT1 Inhibits T-cell Infiltration and Tertiary Lymphoid Structure Formation to Promote Radioimmunotherapy Resistance.Cancer research · 2026Article
- The role of non-coding RNAs in regulating R-loop dynamics in cancer: Mechanisms and therapeutic implications.Acta pharmaceutica Sinica. B · 2026Review
- HELZ-BRCA2 complex resolves R-loops to drive transcription-coupled homologous recombination.Nature communications · 2026Article
- HELZ is a RNA-DNA helicase that resolves R loops to facilitate homologous recombination repair.Nature communications · 2026Article
- MYCN and helicases DDX17 and DDX5 have opposite effects on the production of readthrough-associated chimeric transcripts.Cellular and molecular life sciences : CMLS · 2026Article
- Glutamine Deprivation Triggers Tribbles Homolog 3 Dependent G-Quadruplex Resolution to Maintain DNA Repair and Tumor Survival.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Therapeutic vulnerabilities exposed by the 9p21 loss identified through multiparametric drug screening inform rational combination strategies.NPJ precision oncology · 2026Article
- Resolution of R-loops and transcription-replication conflicts by SETX-BRCA1-BARD1 complex.Nature structural & molecular biology · 2026Article
- When R-Loops Go Awry: Genome Instability and Neurological Diseases.The European journal of neuroscience · 2026Review
- Regulation of R-Loop Dynamics by Proteins and Long Noncoding RNAs: An Emerging Paradigm for Cancer Treatment.Cancer science · 2026Review
- Transcription termination counteracts DNA damage after WEE1 inhibition.Nucleic acids research · 2026Article
- Orchestrating innate immunity through RNA editing and helicase activity: ADAR1, dsRNA sensors, and tumor immune evasion.Frontiers in cell and developmental biology · 2026Review
- Targeting R-loops: diverse RNA helicases in R-loop resolution and their potential as targets for cancer therapy.Frontiers in cell and developmental biology · 2026Review
- Distinct mechanisms of recognition of phosphorylated RNAPII C-terminal domain by BRCT repeats of the BRCA1-BARD1 complex.The Journal of biological chemistry · 2026Article
- MTUS2-AS1 suppression promotes DDX5 protein degradation to enhance the sensitivity of PARP inhibitors in BRCA-wild triple negative breast cancer.International journal of biological sciences · 2026Article
- Age-associated G-quadruplex accumulation and DDX5 loss shape chromatin landscapes in human astrocytes.Research square · 2025Article
- Biochemical Characterization of R-Loop Degradation by Chloroplast-Localized RNase H1 fromInternational journal of molecular sciences · 2025Article
- Evolutionary interplay between viruses and R-loops.FEBS letters · 2025Review
66 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Aberrant transcription-associated RNA:DNA hybrid (R-loop) formation often causes catastrophic conflicts during replication, resulting in DNA double-strand breaks and genomic instability. Preventing such conflicts requires hybrid dissolution by helicases and/or RNase H. Little is known about how such helicases are regulated. Herein, we identify DDX5, an RGG/RG motif-containing DEAD-box family RNA helicase, as crucial player in R-loop resolution. In vitro, recombinant DDX5 resolves R-loops in an ATP-dependent manner, leading to R-loop degradation by the XRN2 exoribonuclease. DDX5-deficient cells accumulate R-loops at loci with propensity to form such structures based on RNA:DNA immunoprecipitation (DRIP)-qPCR, causing spontaneous DNA double-strand breaks and hypersensitivity to replication stress. DDX5 associates with XRN2 and resolves R-loops at transcriptional termination regions downstream of poly(A) sites, to facilitate RNA polymerase II release associated with transcriptional termination. Protein arginine methyltransferase 5 (PRMT5) binds and methylates DDX5 at its RGG/RG motif. This motif is required for DDX5 interaction with XRN2 and repression of cellular R-loops, but not essential for DDX5 helicase enzymatic activity. PRMT5-deficient cells accumulate R-loops, resulting in increased formation of γH2AX foci. Our findings exemplify a mechanism by which an RNA helicase is modulated by arginine methylation to resolve R-loops, and its potential role in regulating transcription.
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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.