ArticleNature communications2022
TGS1 mediates 2,2,7-trimethyl guanosine capping of the human telomerase RNA to direct telomerase dependent telomere maintenance.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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
18 citing papers in PubMed, 23 citations in OpenAlex.
- Biogenesis and Regulation of Telomerase during Development and Cancer.Cold Spring Harbor perspectives in biology · 2026Review
- Exosome-mediated decay of unstable long extended precursors of human telomerase RNA is dependent on 5'-cap trimethylation.Genes & development · 2026Article
- Epitranscriptomic control of telomere maintenance.Molecular biology reports · 2026Review
- Extension of replicative lifespan by synthetic engineered telomerase RNA in patient induced pluripotent stem cells.Nature biomedical engineering · 2025Article
- Global analysis by LC-MS/MS ofRNA (New York, N.Y.) · 2025Article
- Review
- A degenerate telomerase RNA directs telomeric DNA synthesis in lepidopteran insects.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A Modular Engineered DNA Nanodevice for Precise Profiling of Telomerase RNA Location and Activity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Targeting telomere dynamics with plant-derived compounds: Molecular strategies against aging.Current research in pharmacology and drug discovery · 2025Review
- RNA modifications: emerging players in the regulation of reproduction and development.Acta biochimica et biophysica Sinica · 2024Review
- Methods that shaped telomerase research.Biogerontology · 2024Review
- The molecular language of RNA 5' ends: guardians of RNA identity and immunity.RNA (New York, N.Y.) · 2024Review
- Advances in understanding telomerase assembly.Biochemical Society transactions · 2023Review
- Coilin and Cajal bodies.Nucleus (Austin, Tex.) · 2023Review
- Telomerase-activated Au@DNA nanomachine for targeted chemo-photodynamic synergistic therapy.RSC medicinal chemistry · 2023Article
- Post-Transcriptional and Post-Translational Modifications in Telomerase Biogenesis and Recruitment to Telomeres.International journal of molecular sciences · 2023Review
- Sequestering the 5'-cap for viral RNA packaging.BioEssays : news and reviews in molecular, cellular and developmental biology · 2022Article
- Telomere biology disorders: time for moving towards the clinic?Trends in molecular medicine · 2022Review
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pathways that direct the selection of the telomerase-dependent or recombination-based, alternative lengthening of telomere (ALT) maintenance pathway in cancer cells are poorly understood. Using human lung cancer cells and tumor organoids we show that formation of the 2,2,7-trimethylguanosine (TMG) cap structure at the human telomerase RNA 5' end by the Trimethylguanosine Synthase 1 (TGS1) is central for recruiting telomerase to telomeres and engaging Cajal bodies in telomere maintenance. TGS1 depletion or inhibition by the natural nucleoside sinefungin impairs telomerase recruitment to telomeres leading to Exonuclease 1 mediated generation of telomere 3' end protrusions that engage in RAD51-dependent, homology directed recombination and the activation of key features of the ALT pathway. This indicates a critical role for 2,2,7-TMG capping of the RNA component of human telomerase (hTR) in enforcing telomerase-dependent telomere maintenance to restrict the formation of telomeric substrates conductive to ALT. Our work introduces a targetable pathway of telomere maintenance that holds relevance for telomere-related diseases such as cancer and aging.
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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 Socratic graph.