ArticleNucleic acids research2024
METTL3 drives telomere targeting of TERRA lncRNA through m6A-dependent R-loop formation: a therapeutic target for ALT-positive neuroblastoma.
Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- The role of R-loops-mediated epigenetic regulation in genome stability maintenance and disease pathogenesis: a systematic review.Epigenetics · 2026Pooled it
- The role of non-coding RNAs in regulating R-loop dynamics in cancer: Mechanisms and therapeutic implications.Acta pharmaceutica Sinica. B · 2026Review
- R-loops and D-loops: a delicate balance in genomic stability and instability.Cell communication and signaling : CCS · 2026Review
- The lncRNA-m6A axis in cancer: a bidirectional regulatory network in tumor progression and therapeutic resistance.Journal of translational medicine · 2026Review
- mCellular & molecular biology letters · 2026Article
- Unveiling the molecular landscape: Long non-coding RNAs in neuroblastoma (Review).Oncology reports · 2026Review
- Emerging roles of RNA mInternational journal of oncology · 2026Review
- Epitranscriptomic control of telomere maintenance.Molecular biology reports · 2026Review
- Targeted therapies in pediatric oncology: A start.Molecular therapy. Oncology · 2026Review
- Mechanisms at the Intersection of lncRNA and m6A Biology.Non-coding RNA · 2026Review
- HNRNPA2B1 as an emerging coordinator of RNA fate in cancer: m6A reading, RNA export, translation reprogramming, and immune-metabolic adaptation.Frontiers in immunology · 2026Review
- Long non-coding RNA RP11-196G11.6 inhibits neuroblastoma progression by regulating the miR-376a-3p/RYBP signaling axis.Oncology letters · 2026Article
- Integrative Bulk and Single-Cell Transcriptome Profiling of Telomere-Related Genes Reveals a Robust Prognostic Signature and Immunotherapeutic Landscape in Neuroblastoma.Journal of Cancer · 2026Article
- Advances in multi-omics research on neuroblastoma.Frontiers in pediatrics · 2026Review
- Late-Onset Preeclampsia is characterised by Accelerated Placental Aging.bioRxiv : the preprint server for biology · 2025Article
- Dual roles of NScience China. Life sciences · 2025Article
- m6A modification of non‑coding RNA: Mechanisms, functions and potential values in human diseases (Review).International journal of molecular medicine · 2025Review
- Core transcriptional regulatory circuit-regulated IGF2BP3 stabilizes E2F2 mRNA via m6A modification in neuroblastoma.Carcinogenesis · 2025Article
- m6A modification in R-loop homeostasis: a potential target for cancer therapeutics.NAR cancer · 2025Review
- Review
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
Abstract
Telomerase-negative tumors maintain telomere length by alternative lengthening of telomeres (ALT), but the underlying mechanism behind ALT remains poorly understood. A proportion of aggressive neuroblastoma (NB), particularly relapsed tumors, are positive for ALT (ALT+), suggesting that a better dissection of the ALT mechanism could lead to novel therapeutic opportunities. TERRA, a long non-coding RNA (lncRNA) derived from telomere ends, localizes to telomeres in a R-loop-dependent manner and plays a crucial role in telomere maintenance. Here we present evidence that RNA modification at the N6 position of internal adenosine (m6A) in TERRA by the methyltransferase METTL3 is essential for telomere maintenance in ALT+ cells, and the loss of TERRA m6A/METTL3 results in telomere damage. We observed that m6A modification is abundant in R-loop enriched TERRA, and the m6A-mediated recruitment of hnRNPA2B1 to TERRA is critical for R-loop formation. Our findings suggest that m6A drives telomere targeting of TERRA via R-loops, and this m6A-mediated R-loop formation could be a widespread mechanism employed by other chromatin-interacting lncRNAs. Furthermore, treatment of ALT+ NB cells with a METTL3 inhibitor resulted in compromised telomere targeting of TERRA and accumulation of DNA damage at telomeres, indicating that METTL3 inhibition may represent a therapeutic approach for ALT+ NB.
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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.