ArticleNature communications2025
Telomerase RNA structural heterogeneity in living human cells detected by DMS-MaPseq.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Differential human telomerase RNA knockdown by antisense oligonucleotides reveals the existence and potential function of a robust RNA domain.RNA (New York, N.Y.) · 2026Article
- Subcellular Localization of Telomerase Reverse Transcriptase Regulates Gene-Specific Modulation of Mitochondrial DNA Copy Number in Neuronal Cells.Molecular neurobiology · 2026Article
- Identification of conserved RNA regulatory switches in living cells using RNA secondary structure ensemble mapping and covariation analysis.Nature biotechnology · 2026Article
- VIRSE: a variational Bayesian framework for RNA structural ensemble inference.Briefings in bioinformatics · 2026Article
- Recent Advances in Chemical Probing Strategies for RNA Structure Determination In Vivo.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Review
- La protein binding to telomerase RNA supports an evolutionary relationship between plant and ciliate telomerase pathways.Nucleic acids research · 2026Article
- RNA Triple Helices: From Structures and Mechanisms to Therapeutic Targets.International journal of biological sciences · 2026Review
- Ribosome-induced mRNA pseudoknot interactions visualized by DMS MaP-Seq.bioRxiv : the preprint server for biology · 2025Article
- Cryo-EM structure of human telomerase dimer reveals H/ACA RNP-mediated dimerization.Science (New York, N.Y.) · 2025Article
- Visualizing RNA structure ensembles by single-molecule correlated chemical probing.Current opinion in structural biology · 2024Review
- Molecular and Evolutionary Analysis of RNA-Protein Interactions in Telomerase Regulation.Non-coding RNA · 2024Review
- Advances in understanding telomerase assembly.Biochemical Society transactions · 2023Review
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8 authors.
Funding
Abstract
Biogenesis of human telomerase requires its RNA subunit (hTR) to fold into a multi-domain architecture that includes the template-pseudoknot (t/PK) and the three-way junction (CR4/5). These hTR domains bind the telomerase reverse transcriptase (hTERT) protein and are essential for telomerase activity. Here, we probe hTR structure in living cells using dimethyl sulfate mutational profiling with sequencing (DMS-MaPseq) and ensemble deconvolution analysis. Approximately 15% of the steady state population of hTR has a CR4/5 conformation lacking features required for hTERT binding. The proportion of hTR CR4/5 folded into the primary functional conformation is independent of hTERT expression levels. Mutations that stabilize the alternative CR4/5 conformation are detrimental to telomerase assembly and activity. Moreover, the alternative CR4/5 conformation is not found in purified telomerase RNP complexes, supporting the hypothesis that only the primary CR4/5 conformer is active. We propose that this misfolded portion of the cellular hTR pool is either slowly refolded or degraded, suggesting that kinetic RNA folding traps studied in vitro may also hinder ribonucleoprotein assembly in vivo.
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