Open Access
Cell Reports, volume 30, issue 5, pages 1358-137200000
Loss of Human TGS1 Hypermethylase Promotes Increased Telomerase RNA and Telomere Elongation
Chen Lu
1
,
Roake Caitlin M
1
,
Galati Alessandra
2
,
Bavasso Francesca
2
,
Micheli Emanuela
2
,
Saggio Isabella
2
,
Schoeftner Stefan
3
,
Cacchione Stefano
2
,
Gatti Maurizio
4
,
Artandi Steven E.
1
,
Raffa Grazia D
2
1
Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA
|
3
Cancer Epigenetic Group, Laboratorio Nazionale Consorzio Interuniversitario Biotecnologie, Trieste, Italy
|
Publication type: Journal Article
Publication date: 2020-02-11
PubMed ID:
32023455
General Biochemistry, Genetics and Molecular Biology
Abstract
SUMMARY Biogenesis of the human telomerase RNA (hTR) involves a complex series of posttranscriptional modifications, including hypermethylation of the 5′ mono-methylguanosine cap to a tri-methylguanosine cap (TMG). How the TMG cap affects hTR maturation is unknown. Here, we show that depletion of trimethylguanosine synthase 1 (TGS1), the enzyme responsible for cap hypermethylation, increases levels of hTR and telomerase. Diminished trimethylation increases hTR association with the cap-binding complex (CBC) and with Sm chaperone proteins. Loss of TGS1 causes an increase in accumulation of mature hTR in both the nucleus and the cytoplasm compared with controls. In TGS1 mutant cells, increased hTR assembles with telomerase reverse transcriptase (TERT) protein to yield elevated active telomerase complexes and increased telomerase activity, resulting in telomere elongation in cultured human cells. Our results show that TGS1-mediated hypermethylation of the hTR cap inhibits hTR accumulation, restrains levels of assembled telomerase, and limits telomere elongation.
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- We do not take into account publications that without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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Chen L. et al. Loss of Human TGS1 Hypermethylase Promotes Increased Telomerase RNA and Telomere Elongation // Cell Reports. 2020. Vol. 30. No. 5. pp. 1358-137200000.
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Chen L., Roake C. M., Galati A., Bavasso F., Micheli E., Saggio I., Schoeftner S., Cacchione S., Gatti M., Artandi S. E., Raffa G. D. Loss of Human TGS1 Hypermethylase Promotes Increased Telomerase RNA and Telomere Elongation // Cell Reports. 2020. Vol. 30. No. 5. pp. 1358-137200000.
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TY - JOUR
DO - 10.1016/j.celrep.2020.01.004
UR - https://doi.org/10.1016%2Fj.celrep.2020.01.004
TI - Loss of Human TGS1 Hypermethylase Promotes Increased Telomerase RNA and Telomere Elongation
T2 - Cell Reports
AU - Chen, Lu
AU - Roake, Caitlin M
AU - Galati, Alessandra
AU - Bavasso, Francesca
AU - Micheli, Emanuela
AU - Saggio, Isabella
AU - Schoeftner, Stefan
AU - Cacchione, Stefano
AU - Gatti, Maurizio
AU - Artandi, Steven E.
AU - Raffa, Grazia D
PY - 2020
DA - 2020/02/11 00:00:00
PB - Elsevier
SP - 1358-137200000
IS - 5
VL - 30
PMID - 32023455
SN - 2211-1247
ER -
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@article{2020_Chen,
author = {Lu Chen and Caitlin M Roake and Alessandra Galati and Francesca Bavasso and Emanuela Micheli and Isabella Saggio and Stefan Schoeftner and Stefano Cacchione and Maurizio Gatti and Steven E. Artandi and Grazia D Raffa},
title = {Loss of Human TGS1 Hypermethylase Promotes Increased Telomerase RNA and Telomere Elongation},
journal = {Cell Reports},
year = {2020},
volume = {30},
publisher = {Elsevier},
month = {feb},
url = {https://doi.org/10.1016%2Fj.celrep.2020.01.004},
number = {5},
pages = {1358--137200000},
doi = {10.1016/j.celrep.2020.01.004}
}
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MLA
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Chen, Lu, et al. “Loss of Human TGS1 Hypermethylase Promotes Increased Telomerase RNA and Telomere Elongation.” Cell Reports, vol. 30, no. 5, Feb. 2020, pp. 1358-137200000. https://doi.org/10.1016%2Fj.celrep.2020.01.004.