ArticleJournal of the American Chemical Society2023
Promoter R-Loops Recruit U2AF1 to Modulate Its Phase Separation and RNA Splicing.
Article in Journal of the American Chemical Society, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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.
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.
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Who cites it
19 citing papers in PubMed, 19 citations in OpenAlex.
- The DNA/RNA Helicase SETX Maintains R-Loop Homeostasis to Promote Chemoresistance in Ovarian Cancer.Cancer science · 2026Article
- G-Quadruplexes: Structural Diversity and Emerging Roles in Biomolecular Condensation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- R-loops and D-loops: a delicate balance in genomic stability and instability.Cell communication and signaling : CCS · 2026Review
- YY1 Interacts with Promoter R-Loops to Regulate Transcription.Journal of the American Chemical Society · 2026Article
- The Tale of the Guanosine Tract in Repeat Expansion Disorders.Molecular neurobiology · 2026Review
- Regulation of transcription by R loop-nucleated transcription condensate assembly.Cell & bioscience · 2026Review
- Natural G-Quadruplex Stabilizers: A Targeted Strategy for Breast Cancer Therapy.Drug design, development and therapy · 2026Review
- Revealing G4 Structures as Drug Targets: Exploring the Potential of Novel Therapeutic Agents.Research (Washington, D.C.) · 2026Review
- Prediction of liquid-liquid phase separation proteins based on protein language model.Briefings in bioinformatics · 2025Article
- The effect of U2AF1 mutation on erythroid differentiation and sensitivity to demethylation drug treatment.Medical oncology (Northwood, London, England) · 2025Article
- SRSF3 undergoes phase separation in lung cancer and is associated with immunity and ferroptosis.Scientific reports · 2025Article
- Review
- Prognostic Significance of R-Loops in Lung Adenocarcinoma: Implications for Immune Response and Drug Sensitivity.Cancer management and research · 2025Article
- Phase separation in DNA repair: orchestrating the cellular response to genomic stability.PeerJ · 2025Review
- Looping forward: exploring R-loop processing and therapeutic potential.FEBS letters · 2025Review
- A Compendium of G-Flipon Biological Functions That Have Experimental Validation.International journal of molecular sciences · 2024Review
- RNA biogenesis and RNA metabolism factors as R-loop suppressors: a hidden role in genome integrity.Genes & development · 2024Review
- A super minigene with a short promoter and truncated introns recapitulates essential features of transcription and splicing regulation of the SMN1 and SMN2 genes.Nucleic acids research · 2024Article
- Shaping Spliceosome Dynamics Through Protein Arginine Methylation.Wiley interdisciplinary reviews. RNAReview
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
R-loops and guanine quadruplexes (G4s) are secondary structures of nucleic acids that are ubiquitously present in cells and are enriched in promoter regions of genes. By employing a bioinformatic approach based on overlap analysis of transcription factor chromatin immunoprecipitation sequencing (ChIP-seq) data sets, we found that many splicing factors, including U2AF1 whose recognition of the 3' splicing site is crucial for pre-mRNA splicing, exhibit pronounced enrichment at endogenous R-loop- and DNA G4-structure loci in promoter regions of human genes. We also revealed that U2AF1 binds directly to R-loops and DNA G4 structures at a low-nM binding affinity. Additionally, we showed the ability of U2AF1 to undergo phase separation, which could be stimulated by binding with R-loops, but not duplex DNA, RNA/DNA hybrid, DNA G4, or single-stranded RNA. We also demonstrated that U2AF1 binds to promoter R-loops in human cells, and this binding competes with U2AF1's interaction with 3' splicing site and leads to augmented distribution of RNA polymerase II (RNAPII) to promoters over gene bodies, thereby modulating cotranscriptional pre-mRNA splicing. Together, we uncovered a group of candidate proteins that can bind to both R-loops and DNA G4s, revealed the direct and strong interactions of U2AF1 with these nucleic acid structures, and established a biochemical rationale for U2AF1's occupancy in gene promoters. We also unveiled that interaction with R-loops promotes U2AF1's phase separation, and our work suggests that U2AF1 modulates pre-mRNA splicing by regulating RNAPII's partition in transcription initiation versus elongation.
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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.