ArticleGenes & development2021
Replication protein A associates with nucleolar R loops and regulates rRNA transcription and nucleolar morphology.
Article in Genes & development, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 24 citations in OpenAlex.
- The identity crisis of cryptic lncRNAs: when non-coding RNAs translate into small peptides.The EMBO journal · 2026Review
- RPA hyperphosphorylation hinders the resolution of R-loops and G-quadruplex-associated R-loops during RAS-driven senescence.Nucleic acids research · 2026Article
- When R-Loops Go Awry: Genome Instability and Neurological Diseases.The European journal of neuroscience · 2026Review
- Article
- HCR-Proxy resolves site-specific proximal RNA microenvironments at subcompartmental resolution.Nucleic acids research · 2026Article
- Early growth response 1 promotes RNA polymerase I-directed transcription and cancer growth by activating RRN3 expression.Communications biology · 2026Article
- Atypical R-loops in cancer: decoding molecular chaos for therapeutic gain.Journal of translational medicine · 2025Review
- Interpreting the Origins and Functions of Noncoding RNAs From the Ribosomal Genes.Journal of cellular physiology · 2025Review
- Participants in Transcription-Replication Conflict and Their Role in Formation and Resolution of R-Loops.International journal of molecular sciences · 2025Review
- The relevance of RNA-DNA interactions as regulators of physiological functions.Pflugers Archiv : European journal of physiology · 2025Review
- FUBP3 enhances HIV-1 transcriptional activity and regulates immune response pathways in T cells.Molecular therapy. Nucleic acids · 2025Article
- GPATCH4 functions as a regulator of nucleolar R-loops in hepatocellular carcinoma cells.Nucleic acids research · 2025Article
- Review
- Article
- RPA transforms RNase H1 to a bidirectional exoribonuclease for processive RNA-DNA hybrid cleavage.Nature communications · 2024Article
- Senataxin deficiency disrupts proteostasis through nucleolar ncRNA-driven protein aggregation.The Journal of cell biology · 2024Article
- Human Bocavirus 1 NP1 acts as an ssDNA-binding protein to help AAV2 DNA replication and cooperates with RPA to regulate AAV2 capsid expression.Journal of virology · 2024Article
- ATR phosphorylates DHX9 at serine 321 to suppress R-loop accumulation upon genotoxic stress.Nucleic acids research · 2024Article
- Article
- A nucleolar long "non-coding" RNA encodes a novel protein that functions in response to stress.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The nucleolus is an important cellular compartment in which ribosomal RNAs (rRNAs) are transcribed and where certain stress pathways that are crucial for cell growth are coordinated. Here we report novel functions of the DNA replication and repair factor replication protein A (RPA) in control of nucleolar homeostasis. We show that loss of the DNA:RNA helicase senataxin (SETX) promotes RPA nucleolar localization, and that this relocalization is dependent on the presence of R loops. Notably, this nucleolar RPA phenotype was also observed in the presence of camptothecin (CPT)-induced genotoxic stress, as well as in SETX-deficient AOA2 patient fibroblasts. Extending these results, we found that RPA is recruited to rDNA following CPT treatment, where RPA prevents R-loop-induced DNA double-strand breaks. Furthermore, we show that loss of RPA significantly decreased 47S pre-rRNA levels, which was accompanied by increased expression of both RNAP II-mediated "promoter and pre-rRNA antisense" RNA as well as RNAP I-transcribed intragenic spacer RNAs. Finally, and likely reflecting the above, we found that loss of RPA promoted nucleolar structural disorganization, characterized by the appearance of reduced size nucleoli. Our findings both indicate new roles for RPA in nucleoli through pre-rRNA transcriptional control and also emphasize that RPA function in nucleolar homeostasis is linked to R-loop resolution under both physiological and pathological conditions.
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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.