Open Access
Cell Reports, volume 13, issue 10, pages 2244-2257
A Polyadenylation-Dependent 3′ End Maturation Pathway Is Required for the Synthesis of the Human Telomerase RNA
Nguyen D.
1
,
Grenier St Sauveur Valérie
1
,
Bergeron Danny
1
,
Dupuis Sandoval Fabien
1
,
Scott Michelle
1
,
Bachand François
1
1
RNA Group, Department of Biochemistry, Université de Sherbrooke, Sherbrooke, QC, J1E 4K8 Canada
|
Publication type: Journal Article
Publication date: 2015-12-01
General Biochemistry, Genetics and Molecular Biology
Abstract
Telomere maintenance by the telomerase reverse transcriptase requires a noncoding RNA subunit that acts as a template for the synthesis of telomeric repeats. In humans, the telomerase RNA (hTR) is a non-polyadenylated transcript produced from an independent transcriptional unit. As yet, the mechanism and factors responsible for hTR 3' end processing have remained largely unknown. Here, we show that hTR is matured via a polyadenylation-dependent pathway that relies on the nuclear poly(A)-binding protein PABPN1 and the poly(A)-specific RNase PARN. Depletion of PABPN1 and PARN results in telomerase RNA deficiency and the accumulation of polyadenylated precursors. Accordingly, a deficiency in PABPN1 leads to impaired telomerase activity and telomere shortening. In contrast, we find that hTRAMP-dependent polyadenylation and exosome-mediated degradation function antagonistically to hTR maturation, thereby limiting telomerase RNA accumulation. Our findings unveil a critical requirement for RNA polyadenylation in telomerase RNA biogenesis, providing alternative approaches for telomerase inhibition in cancer.
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- Statistics recalculated weekly.
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Nguyen D. et al. A Polyadenylation-Dependent 3′ End Maturation Pathway Is Required for the Synthesis of the Human Telomerase RNA // Cell Reports. 2015. Vol. 13. No. 10. pp. 2244-2257.
GOST all authors (up to 50)
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Nguyen D., Grenier St Sauveur V., Bergeron D., Dupuis Sandoval F., Scott M., Bachand F. A Polyadenylation-Dependent 3′ End Maturation Pathway Is Required for the Synthesis of the Human Telomerase RNA // Cell Reports. 2015. Vol. 13. No. 10. pp. 2244-2257.
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TY - JOUR
DO - 10.1016/j.celrep.2015.11.003
UR - https://doi.org/10.1016%2Fj.celrep.2015.11.003
TI - A Polyadenylation-Dependent 3′ End Maturation Pathway Is Required for the Synthesis of the Human Telomerase RNA
T2 - Cell Reports
AU - Nguyen, D.
AU - Grenier St Sauveur, Valérie
AU - Bergeron, Danny
AU - Dupuis Sandoval, Fabien
AU - Scott, Michelle
AU - Bachand, François
PY - 2015
DA - 2015/12/01 00:00:00
PB - Elsevier
SP - 2244-2257
IS - 10
VL - 13
SN - 2211-1247
ER -
Cite this
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@article{2015_Nguyen,
author = {D. Nguyen and Valérie Grenier St Sauveur and Danny Bergeron and Fabien Dupuis Sandoval and Michelle Scott and François Bachand},
title = {A Polyadenylation-Dependent 3′ End Maturation Pathway Is Required for the Synthesis of the Human Telomerase RNA},
journal = {Cell Reports},
year = {2015},
volume = {13},
publisher = {Elsevier},
month = {dec},
url = {https://doi.org/10.1016%2Fj.celrep.2015.11.003},
number = {10},
pages = {2244--2257},
doi = {10.1016/j.celrep.2015.11.003}
}
Cite this
MLA
Copy
Nguyen, D., et al. “A Polyadenylation-Dependent 3′ End Maturation Pathway Is Required for the Synthesis of the Human Telomerase RNA.” Cell Reports, vol. 13, no. 10, Dec. 2015, pp. 2244-2257. https://doi.org/10.1016%2Fj.celrep.2015.11.003.