ArticleNucleic acids research2023
The THO complex counteracts TERRA R-loop-mediated telomere fragility in telomerase+ cells and telomeric recombination in ALT+ cells.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Epigenetic control of telomeric RNA maintains heterochromatin in telomerase-driven cancers.Signal transduction and targeted therapy · 2026Article
- Structural organization and function of telomeric chromatin.Nature cell biology · 2026Review
- Chronic sublethal exposure to methylmercury lengthens telomeres in developing zebra finches.Environmental pollution (Barking, Essex : 1987) · 2025Article
- Beyond the ends: potential implications of telomeric repeat-containing RNA (TERRA) for CNS diseases.Journal of molecular cell biology · 2025Review
- A pan-cancer analysis of the oncogenic and immunological roles of THOC3 in human cancer.Scientific reports · 2025Article
- The paradox of R-loops: guardians of the genome or drivers of disease?Genome research · 2025Review
- Possible role of human ribonuclease dicer in the regulation of R loops.FEBS open bio · 2025Review
- Atypical R-loops in cancer: decoding molecular chaos for therapeutic gain.Journal of translational medicine · 2025Review
- TERRA R-loops trigger a switch in telomere maintenance towards break-induced replication and PRIMPOL-dependent repair.The EMBO journal · 2025Article
- Elevated reactive oxygen species can drive the alternative lengthening of telomeres pathway in ATRX-null cancers.Nucleic acids research · 2025Article
- Identification of modulators of the ALT pathway through a native FISH-based optical screen.Cell reports · 2025Article
- Identification of Novel Modulators of the ALT Pathway Through a Native FISH-Based Optical Screen.bioRxiv : the preprint server for biology · 2024Article
- RNA biogenesis and RNA metabolism factors as R-loop suppressors: a hidden role in genome integrity.Genes & development · 2024Review
- METTL3 drives telomere targeting of TERRA lncRNA through m6A-dependent R-loop formation: a therapeutic target for ALT-positive neuroblastoma.Nucleic acids research · 2024Article
- Telomeric repeat-containing RNA is dysregulated in acute myeloid leukemia.Blood advances · 2023Article
- TERRA R-loops connect and protect sister telomeres in mitosis.Cell reports · 2023Article
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2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Telomeres are the nucleoprotein structures at the ends of linear chromosomes. Telomeres are transcribed into long non-coding Telomeric Repeat-Containing RNA (TERRA), whose functions rely on its ability to associate with telomeric chromatin. The conserved THO complex (THOC) was previously identified at human telomeres. It links transcription with RNA processing, decreasing the accumulation of co-transcriptional DNA:RNA hybrids throughout the genome. Here, we explore the role of THOC at human telomeres, as a regulator of TERRA localization to chromosome ends. We show that THOC counteracts TERRA association with telomeres via R-loops formed co-transcriptionally and also post-transcriptionally, in trans. We demonstrate that THOC binds nucleoplasmic TERRA, and that RNaseH1 loss, which increases telomeric R-loops, promotes THOC occupancy at telomeres. Additionally, we show that THOC counteracts lagging and mainly leading strand telomere fragility, suggesting that TERRA R-loops can interfere with replication fork progression. Finally, we observed that THOC suppresses telomeric sister-chromatid exchange and C-circle accumulation in ALT cancer cells, which maintain telomeres by recombination. Altogether, our findings reveal crucial roles of THOC in telomeric homeostasis through the co- and post-transcriptional regulation of TERRA R-loops.
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