ArticleMolecular and cellular biology2008
Disease-associated human telomerase RNA variants show loss of function for telomere synthesis without dominant-negative interference.
Article in Molecular and cellular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- RTEL1 mutation modifies dyskeratosis congenita caused by a telomerase RNA template mutation.Nature communications · 2026Article
- Cryo-EM structure of human telomerase dimer reveals H/ACA RNP-mediated dimerization.Science (New York, N.Y.) · 2025Article
- A persistent variant telomere sequence in a human pedigree.Nature communications · 2024Article
- How Structural Features Define Biogenesis and Function of Human Telomerase RNA Primary Transcript.Biomedicines · 2022Review
- Systematics for types and effects of RNA variations.RNA biology · 2021Article
- Progress in Human and Tetrahymena Telomerase Structure Determination.Annual review of biophysics · 2017Review
- Article
- Many disease-associated variants of hTERT retain high telomerase enzymatic activity.Nucleic acids research · 2013Article
- Structure of active dimeric human telomerase.Nature structural & molecular biology · 2013Article
- Telomere lengthening and other functions of telomerase.Acta naturae · 2012Article
- Dyskeratosis congenita as a disorder of telomere maintenance.Mutation research · 2012Review
- Single-stranded DNA repeat synthesis by telomerase.Current opinion in chemical biology · 2011Review
- Human telomerase domain interactions capture DNA for TEN domain-dependent processive elongation.Molecular cell · 2011Article
- The 5' guanosine tracts of human telomerase RNA are recognized by the G-quadruplex binding domain of the RNA helicase DHX36 and function to increase RNA accumulation.Molecular and cellular biology · 2011Article
- InTERTpreting telomerase structure and function.Nucleic acids research · 2010Review
- Specificity and stoichiometry of subunit interactions in the human telomerase holoenzyme assembled in vivo.Molecular and cellular biology · 2010Article
- Genetic Variations in Telomere Maintenance, with Implications on Tissue Renewal Capacity and Chronic Disease Pathologies.Current pharmacogenomics and personalized medicine · 2010Article
- Investigation of human telomerase holoenzyme assembly, activity, and processivity using disease-linked subunit variants.The Journal of biological chemistry · 2010Article
- An RPA-related sequence-specific DNA-binding subunit of telomerase holoenzyme is required for elongation processivity and telomere maintenance.Molecular cell · 2009Article
- Telomere dysfunction in human diseases: the long and short of it!International journal of clinical and experimental pathology · 2009Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
Abstract
Telomerase adds simple-sequence repeats to chromosome ends to offset the terminal sequence loss inherent in each cycle of genome replication. Inherited mutations in genes encoding subunits of the human telomerase holoenzyme give rise to disease phenotypes including hematopoietic failure and pulmonary fibrosis. Disease-associated variants of the human telomerase RNA are expressed in heterozygous combination with wild-type telomerase RNA. Here, we exploit a sensitized human primary cell assay system to investigate the biological function of disease-linked telomerase RNA variants and their impact on the function of coexpressed wild-type telomerase RNA. We find that telomerase RNA variants discovered in patients with dyskeratosis congenita or aplastic anemia show loss of function without any indication of dominant-negative impact on telomere maintenance by the coexpressed wild-type RNA. To reconcile this result with contradictory findings from reconstitution assays in vitro, we demonstrate that the lack of dominant-negative impact on telomere maintenance correlates with physiological assembly of active human telomerase holoenzyme ribonucleoproteins harboring monomers rather than higher-order multimers of telomerase RNA and telomerase reverse transcriptase. These findings support loss of function of telomerase RNA as a general mechanism of human disease.
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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.