The telomerase reverse transcriptase is limiting and necessary for telomerase function in vivo
Open accessAbstract
Mammalian telomerase is essential for the maintenance of telomere length [1-5]. Its catalytic core comprises a reverse transcriptase component (TERT) and an RNA component. While the biochemical role of mammalian TERT is well established [6-11], it is unknown whether it is sufficient for telomere-length maintenance, chromosome stability or other cellular processes. Cells from mice in which the mTert gene had been disrupted showed progressive loss of telomere DNA, a phenotype similar to cells in which the gene encoding the telomerase RNA component (mTR) has been disrupted [1,12]. On prolonged growth, mTert-deficient embryonic stem (ES) cells exhibited genomic instability, aneuploidy and telomeric fusions. ES cells heterozygous for the mTert disruption also showed telomere attrition, a phenotype that differs from heterozygous mTR cells [12]. Thus, telomere maintenance in mammals is carried out by a single, limiting TERT.
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Telomerase plays a crucial role in self-renewal of adult stem cells in high-turnover tissues such as blood, liver, skin, and testis.
“The generation of mouse models lacking telomerase activity, TERT and Terc knockout mice (Blasco et al., 1997; Liu et al., 2000) previously resulted in the demonstration that telomerase plays a crucial role in self-renewal of adult stem cells in high turnover tissues such as blood, liver, skin and testis (Allsopp et al., 2003; Lee et al., 1998).”
From Short Telomeres and Stem Cell Exhaustion Model Duchenne Muscular Dystrophy in mdx/mTR Mice (2010) · cites this paper as Liu et al., 2000
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“1C), which is consistent with previous findings ( Liu et al., 2000 ; Strong et al., 2011 ).”
ResultTelomeres, a busy platform for cell signaling.
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Self-citation
- Authors
- Liu, Y., Snow, B. E., Hande, M. P., Yeung, D., Erdmann, N. J., Wakeham, A., Itie, A., Siderovski, D. P., Lansdorp, P. M., Robinson, M. O., & Harrington, L.
- Affiliations
- University of Toronto (CA)
- Columbia University Irving Medical Center (US)
- Amgen (United States) (US)
- University of North Carolina at Chapel Hill (US)
- University of British Columbia (CA)
- Corresponding author
- Harrington, L
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2000-11
- Volume
- 10
- Issue
- 22
- Pages
- 1459-1462
- ISSN
- 0960-9822 (ISSN-L)
- OpenAlex
- W2086089050
- Cited by
- 244
- References
- 9
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 5 · 2023: 10 · 2022: 7 · 2021: 5 · 2020: 6 · 2019: 7 · 2018: 6 · 2017: 2 · 2016: 11 · 2015: 9 · 2014: 6 · 2013: 13 · 2012: 9
- FWCI
- 7.76
- Type
- journal article
- Language
- en
- Update notices
- erratum (2001-06-01)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG8422117)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- telomerase reverse transcriptase, telomerase RNA, telomere maintenance, telomerase deficiency, telomere shortening, telomerase reconstitution, telomerase RNA template, neural tube closure, aging, cancer, longevity, stress response
- MeSH terms
- Animals, Cell Line, DNA-Binding Proteins, RNA, Telomere, Gene Targeting, Telomerase, Mice
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