Open Access
Journal of Clinical Investigation, volume 126, issue 9, pages 3377-3382
Posttranscriptional manipulation of TERC reverses molecular hallmarks of telomere disease
Boyraz Baris
1, 2
,
Moon Diane H.
3
,
Segal Matthew
3
,
Muosieyiri Maud Z.
3
,
Aykanat Asli
3
,
Tai Albert
4
,
Cahan Patrick
,
Agarwal Suneet
3
Publication type: Journal Article
Publication date: 2016-08-01
Journal:
Journal of Clinical Investigation
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 15.9
ISSN: 00219738, 15588238
DOI:
10.1172/JCI87547
PubMed ID:
27482890
General Medicine
Abstract
The telomerase RNA component (TERC) is a critical determinant of cellular self-renewal. Poly(A)-specific ribonuclease (PARN) is required for posttranscriptional maturation of TERC. PARN mutations lead to incomplete 3' end processing and increased destruction of nascent TERC RNA transcripts, resulting in telomerase deficiency and telomere diseases. Here, we determined that overexpression of TERC increased telomere length in PARN-deficient cells and hypothesized that decreasing posttranscriptional 3' oligo-adenylation of TERC would counteract the deleterious effects of PARN mutations. Inhibition of the noncanonical poly(A) polymerase PAP-associated domain-containing 5 (PAPD5) increased TERC levels in PARN-mutant patient cells. PAPD5 inhibition was also associated with increases in TERC stability, telomerase activity, and telomere elongation. Our results demonstrate that manipulating posttranscriptional regulatory pathways may be a potential strategy to reverse the molecular hallmarks of telomere disease.
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GOST
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Boyraz B. et al. Posttranscriptional manipulation of TERC reverses molecular hallmarks of telomere disease // Journal of Clinical Investigation. 2016. Vol. 126. No. 9. pp. 3377-3382.
GOST all authors (up to 50)
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Boyraz B., Moon D. H., Segal M., Muosieyiri M. Z., Aykanat A., Tai A., Cahan P., Agarwal S. Posttranscriptional manipulation of TERC reverses molecular hallmarks of telomere disease // Journal of Clinical Investigation. 2016. Vol. 126. No. 9. pp. 3377-3382.
Cite this
RIS
Copy
TY - JOUR
DO - 10.1172/JCI87547
UR - https://doi.org/10.1172%2FJCI87547
TI - Posttranscriptional manipulation of TERC reverses molecular hallmarks of telomere disease
T2 - Journal of Clinical Investigation
AU - Boyraz, Baris
AU - Moon, Diane H.
AU - Segal, Matthew
AU - Muosieyiri, Maud Z.
AU - Aykanat, Asli
AU - Tai, Albert
AU - Cahan, Patrick
AU - Agarwal, Suneet
PY - 2016
DA - 2016/08/01 00:00:00
PB - American Society for Clinical Investigation
SP - 3377-3382
IS - 9
VL - 126
PMID - 27482890
SN - 0021-9738
SN - 1558-8238
ER -
Cite this
BibTex
Copy
@article{2016_Boyraz,
author = {Baris Boyraz and Diane H. Moon and Matthew Segal and Maud Z. Muosieyiri and Asli Aykanat and Albert Tai and Patrick Cahan and Suneet Agarwal},
title = {Posttranscriptional manipulation of TERC reverses molecular hallmarks of telomere disease},
journal = {Journal of Clinical Investigation},
year = {2016},
volume = {126},
publisher = {American Society for Clinical Investigation},
month = {aug},
url = {https://doi.org/10.1172%2FJCI87547},
number = {9},
pages = {3377--3382},
doi = {10.1172/JCI87547}
}
Cite this
MLA
Copy
Boyraz, Baris, et al. “Posttranscriptional manipulation of TERC reverses molecular hallmarks of telomere disease.” Journal of Clinical Investigation, vol. 126, no. 9, Aug. 2016, pp. 3377-3382. https://doi.org/10.1172%2FJCI87547.