Open Access
Open access
Blood, volume 124, issue 25, pages 3675-3684

An antiapoptotic role for telomerase RNA in human immune cells independent of telomere integrity or telomerase enzymatic activity

Gazzaniga Francesca S 1
Blackburn Elizabeth 1
1
 
Department of Biophysics and Biochemistry, University of California, San Francisco, San Francisco, CA
Publication typeJournal Article
Publication date2014-12-11
Journal: Blood
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor20.3
ISSN00064971, 15280020
Biochemistry
Cell Biology
Immunology
Hematology
Abstract
Telomerase is a ribonucleoprotein complex that adds telomeric DNA to the ends of linear chromosomes. It contains two core canonical components: the essential RNA component, hTR, which provides the template for DNA synthesis, and the reverse transcriptase protein component, hTERT. Low telomerase activity in circulating peripheral blood mononuclear cells has been associated with a variety of diseases. It is unknown, however, whether telomerase, in addition to its long-term requirement for telomere maintenance, is also necessary for short-term immune cell proliferation and survival. We report that overexpression of enzymatically inactive hTR mutants protected against dexamethasone-induced apoptosis in stimulated CD4 T cells. Furthermore, hTR knockdown reproducibly induced apoptosis in the absence of any detectable telomere shortening or DNA damage response. In contrast, hTERT knockdown did not induce apoptosis. Strikingly, overexpression of hTERT protein caused apoptosis that was rescued by overexpression of enzymatically inactive hTR mutants. Hence, we propose that hTR can function as a noncoding RNA that protects from apoptosis independent of its function in telomerase enzymatic activity and long-term telomere maintenance in normal human immune cells. These results imply that genetic or environmental factors that alter hTR levels can directly affect immune cell function to influence health and disease.

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GOST |
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GOST Copy
Gazzaniga F. S., Blackburn E. An antiapoptotic role for telomerase RNA in human immune cells independent of telomere integrity or telomerase enzymatic activity // Blood. 2014. Vol. 124. No. 25. pp. 3675-3684.
GOST all authors (up to 50) Copy
Gazzaniga F. S., Blackburn E. An antiapoptotic role for telomerase RNA in human immune cells independent of telomere integrity or telomerase enzymatic activity // Blood. 2014. Vol. 124. No. 25. pp. 3675-3684.
RIS |
Cite this
RIS Copy
TY - JOUR
DO - 10.1182/blood-2014-06-582254
UR - https://doi.org/10.1182%2Fblood-2014-06-582254
TI - An antiapoptotic role for telomerase RNA in human immune cells independent of telomere integrity or telomerase enzymatic activity
T2 - Blood
AU - Gazzaniga, Francesca S
AU - Blackburn, Elizabeth
PY - 2014
DA - 2014/12/11 00:00:00
PB - American Society of Hematology
SP - 3675-3684
IS - 25
VL - 124
PMID - 25320237
SN - 0006-4971
SN - 1528-0020
ER -
BibTex |
Cite this
BibTex Copy
@article{2014_Gazzaniga,
author = {Francesca S Gazzaniga and Elizabeth Blackburn},
title = {An antiapoptotic role for telomerase RNA in human immune cells independent of telomere integrity or telomerase enzymatic activity},
journal = {Blood},
year = {2014},
volume = {124},
publisher = {American Society of Hematology},
month = {dec},
url = {https://doi.org/10.1182%2Fblood-2014-06-582254},
number = {25},
pages = {3675--3684},
doi = {10.1182/blood-2014-06-582254}
}
MLA
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MLA Copy
Gazzaniga, Francesca S., and Elizabeth Blackburn. “An antiapoptotic role for telomerase RNA in human immune cells independent of telomere integrity or telomerase enzymatic activity.” Blood, vol. 124, no. 25, Dec. 2014, pp. 3675-3684. https://doi.org/10.1182%2Fblood-2014-06-582254.
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