Open Access

Nature Structural and Molecular Biology, volume 23, issue 4, pages 286-292

Inhibition of telomerase RNA decay rescues telomerase deficiency caused by dyskerin or PARN defects

Shukla Siddharth ¹

Schmidt Jens C ¹

Goldfarb Katherine C ¹

Cech Thomas R ^{1, 2}

Parker Roy ^{1, 2}

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Department of Chemistry & Biochemistry, University of Colorado, Boulder, USA |

Howard Hughes Medical Institute, Chevy Chase, USA |

Publication type: Journal Article

Publication date: 2016-03-07

Springer Nature

Journal: Nature Structural and Molecular Biology

Quartile SCImago

Quartile WOS

Impact factor: 16.8

ISSN: 15459993, 15459985

DOI: 10.1038/nsmb.3184

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PubMed ID: 26950371

Molecular Biology

Structural Biology

Abstract

Mutations in the human telomerase RNA component (hTR), the telomerase ribonucleoprotein component dyskerin (DKC1) and the poly(A) RNase (PARN) can lead to reduced levels of hTR and to dyskeratosis congenita (DC). However, the enzymes and mechanisms responsible for hTR degradation are unknown. We demonstrate that defects in dyskerin binding lead to hTR degradation by PAPD5-mediated oligoadenylation, which promotes 3′-to-5′ degradation by EXOSC10, as well as decapping and 5′-to-3′ decay by the cytoplasmic DCP2 and XRN1 enzymes. PARN increased hTR levels by deadenylating hTR, thereby limiting its degradation by EXOSC10. Telomerase activity and proper hTR localization in dyskerin- or PARN-deficient cells were rescued by knockdown of DCP2 and/or EXOSC10. Prevention of hTR RNA decay also led to a rescue of localization of DC-associated hTR mutants. These results suggest that inhibition of RNA decay pathways might be a useful therapy for some telomere pathologies.

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Cold Spring Harbor Laboratory	Cold Spring Harbor Laboratory, 4, 4.76% Cold Spring Harbor Laboratory 4 publications, 4.76%
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American Society of Hematology	American Society of Hematology, 2, 2.38% American Society of Hematology 2 publications, 2.38%
Proceedings of the National Academy of Sciences (PNAS)	Proceedings of the National Academy of Sciences (PNAS), 2, 2.38% Proceedings of the National Academy of Sciences (PNAS) 2 publications, 2.38%
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American Society for Clinical Investigation	American Society for Clinical Investigation, 1, 1.19% American Society for Clinical Investigation 1 publication, 1.19%
American Thoracic Society	American Thoracic Society, 1, 1.19% American Thoracic Society 1 publication, 1.19%
The Royal Society	The Royal Society, 1, 1.19% The Royal Society 1 publication, 1.19%
American Chemical Society (ACS)	American Chemical Society (ACS), 1, 1.19% American Chemical Society (ACS) 1 publication, 1.19%
Canadian Science Publishing	Canadian Science Publishing, 1, 1.19% Canadian Science Publishing 1 publication, 1.19%
American Association for the Advancement of Science (AAAS)	American Association for the Advancement of Science (AAAS), 1, 1.19% American Association for the Advancement of Science (AAAS) 1 publication, 1.19%
EMBO press	EMBO press, 1, 1.19% EMBO press 1 publication, 1.19%
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Portland Press	Portland Press, 1, 1.19% Portland Press 1 publication, 1.19%
	2 4 6 8 10 12 14 16

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GOST Copy

Shukla S. et al. Inhibition of telomerase RNA decay rescues telomerase deficiency caused by dyskerin or PARN defects // Nature Structural and Molecular Biology. 2016. Vol. 23. No. 4. pp. 286-292.

GOST all authors (up to 50) Copy

Shukla S., Schmidt J. C., Goldfarb K. C., Cech T. R., Parker R. Inhibition of telomerase RNA decay rescues telomerase deficiency caused by dyskerin or PARN defects // Nature Structural and Molecular Biology. 2016. Vol. 23. No. 4. pp. 286-292.

RIS |

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RIS Copy

TY - JOUR

DO - 10.1038/nsmb.3184

UR - https://doi.org/10.1038%2Fnsmb.3184

TI - Inhibition of telomerase RNA decay rescues telomerase deficiency caused by dyskerin or PARN defects

T2 - Nature Structural and Molecular Biology

AU - Shukla, Siddharth

AU - Schmidt, Jens C

AU - Goldfarb, Katherine C

AU - Cech, Thomas R

AU - Parker, Roy

PY - 2016

DA - 2016/03/07 00:00:00

PB - Springer Nature

SP - 286-292

IS - 4

VL - 23

PMID - 26950371

SN - 1545-9993

SN - 1545-9985

ER -

BibTex |

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BibTex Copy

@article{2016_Shukla,

author = {Siddharth Shukla and Jens C Schmidt and Katherine C Goldfarb and Thomas R Cech and Roy Parker},

title = {Inhibition of telomerase RNA decay rescues telomerase deficiency caused by dyskerin or PARN defects},

journal = {Nature Structural and Molecular Biology},

year = {2016},

volume = {23},

publisher = {Springer Nature},

month = {mar},

url = {https://doi.org/10.1038%2Fnsmb.3184},

number = {4},

pages = {286--292},

doi = {10.1038/nsmb.3184}

}

MLA

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MLA Copy

Shukla, Siddharth, et al. “Inhibition of telomerase RNA decay rescues telomerase deficiency caused by dyskerin or PARN defects.” Nature Structural and Molecular Biology, vol. 23, no. 4, Mar. 2016, pp. 286-292. https://doi.org/10.1038%2Fnsmb.3184.

Found error?

Publisher

Springer Nature

Journal

Nature Structural and Molecular Biology

Quartile SCImago

Quartile WOS

Impact factor

16.8

ISSN

15459993 (Print)
15459985 (Electronic)