The Experts below are selected from a list of 2055 Experts worldwide ranked by ideXlab platform
Suneet Agarwal - One of the best experts on this subject based on the ideXlab platform.
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poly a specific ribonuclease parn mediates 3 end maturation of the Telomerase RNA Component
Nature Genetics, 2015Co-Authors: Diane H Moon, Matthew Segal, Baris Boyraz, Eva C Guinan, Inga Hofmann, Patrick Cahan, Albert K Tai, Suneet AgarwalAbstract:Mutations in the PARN gene (encoding poly(A)-specific ribonuclease) cause telomere diseases including familial idiopathic pulmonary fibrosis (IPF) and dyskeratosis congenita, but how PARN deficiency impairs telomere maintenance is unclear. Here, using somatic cells and induced pluripotent stem cells (iPSCs) from patients with dyskeratosis congenita with PARN mutations, we show that PARN is required for the 3'-end maturation of the Telomerase RNA Component (TERC). Patient-derived cells as well as immortalized cells in which PARN is disrupted show decreased levels of TERC. Deep sequencing of TERC RNA 3' termini shows that PARN is required for removal of post-transcriptionally acquired oligo(A) tails that target nuclear RNAs for degradation. Diminished TERC levels and the increased proportion of oligo(A) forms of TERC are normalized by restoring PARN, which is limiting for TERC maturation in cells. Our results demonstrate a new role for PARN in the biogenesis of TERC and provide a mechanism linking PARN mutations to telomere diseases.
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telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients
Nature, 2010Co-Authors: Suneet Agarwal, Erin M Mcloughlin, Junjiu Huang, Inhyun Park, Justine D MillerAbstract:Patients with dyskeratosis congenita, a disorder of telomere maintenance, suffer degeneration of multiple tissues. Agarwal et al. use iPS (induced pluripotent stem) cell technology to study the mechanisms underlying the disease in humans, and in doing so they discover that reprogramming restores telomere elongation in dyskeratosis congenita cells despite genetic lesions affecting Telomerase. The reprogrammed dyskeratosis congenita cells were able to overcome a critical limitation in Telomerase RNA Component (TERC) levels to restore telomere maintenance and self-renewal, and multiple Telomerase Components are targeted by pluripotency-associated transcription factors. Strategies designed to increase TERC expression may therefore be therapeutically beneficial in dyskeratosis congenita patients. Here, iPS cell technology is used to study the mechanisms underlying dyskeratosis congenita in humans. Reprogramming restores telomere elongation in dyskeratosis congenita cells despite genetic lesions affecting Telomerase. The reprogrammed cells were able to overcome a critical limitation in Telomerase RNA Component (TERC) levels to restore telomere maintenance and self-renewal, and multiple Telomerase Components are targeted by pluripotency-associated transcription factors. Patients with dyskeratosis congenita (DC), a disorder of telomere maintenance, suffer degeneration of multiple tissues1,2,3. Patient-specific induced pluripotent stem (iPS) cells4 represent invaluable in vitro models for human degenerative disorders like DC. A cardinal feature of iPS cells is acquisition of indefinite self-renewal capacity, which is accompanied by induction of the Telomerase reverse transcriptase gene (TERT)5,6,7. We investigated whether defects in Telomerase function would limit derivation and maintenance of iPS cells from patients with DC. Here we show that reprogrammed DC cells overcome a critical limitation in Telomerase RNA Component (TERC) levels to restore telomere maintenance and self-renewal. We discovered that TERC upregulation is a feature of the pluripotent state, that several Telomerase Components are targeted by pluripotency-associated transcription factors, and that in autosomal dominant DC, transcriptional silencing accompanies a 3′ deletion at the TERC locus. Our results demonstrate that reprogramming restores telomere elongation in DC cells despite genetic lesions affecting Telomerase, and show that strategies to increase TERC expression may be therapeutically beneficial in DC patients.
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telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients
Nature, 2010Co-Authors: Suneet Agarwal, Erin M Mcloughlin, Junjiu Huang, Inhyun Park, Yuinhan LohAbstract:Patients with dyskeratosis congenita (DC), a disorder of telomere maintenance, suffer degeneration of multiple tissues. Patient-specific induced pluripotent stem (iPS) cells represent invaluable in vitro models for human degenerative disorders like DC. A cardinal feature of iPS cells is acquisition of indefinite self-renewal capacity, which is accompanied by induction of the Telomerase reverse transcriptase gene (TERT). We investigated whether defects in Telomerase function would limit derivation and maintenance of iPS cells from patients with DC. Here we show that reprogrammed DC cells overcome a critical limitation in Telomerase RNA Component (TERC) levels to restore telomere maintenance and self-renewal. We discovered that TERC upregulation is a feature of the pluripotent state, that several Telomerase Components are targeted by pluripotency-associated transcription factors, and that in autosomal dominant DC, transcriptional silencing accompanies a 3' deletion at the TERC locus. Our results demonstrate that reprogramming restores telomere elongation in DC cells despite genetic lesions affecting Telomerase, and show that strategies to increase TERC expression may be therapeutically beneficial in DC patients.
Inhyun Park - One of the best experts on this subject based on the ideXlab platform.
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telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients
Nature, 2010Co-Authors: Suneet Agarwal, Erin M Mcloughlin, Junjiu Huang, Inhyun Park, Justine D MillerAbstract:Patients with dyskeratosis congenita, a disorder of telomere maintenance, suffer degeneration of multiple tissues. Agarwal et al. use iPS (induced pluripotent stem) cell technology to study the mechanisms underlying the disease in humans, and in doing so they discover that reprogramming restores telomere elongation in dyskeratosis congenita cells despite genetic lesions affecting Telomerase. The reprogrammed dyskeratosis congenita cells were able to overcome a critical limitation in Telomerase RNA Component (TERC) levels to restore telomere maintenance and self-renewal, and multiple Telomerase Components are targeted by pluripotency-associated transcription factors. Strategies designed to increase TERC expression may therefore be therapeutically beneficial in dyskeratosis congenita patients. Here, iPS cell technology is used to study the mechanisms underlying dyskeratosis congenita in humans. Reprogramming restores telomere elongation in dyskeratosis congenita cells despite genetic lesions affecting Telomerase. The reprogrammed cells were able to overcome a critical limitation in Telomerase RNA Component (TERC) levels to restore telomere maintenance and self-renewal, and multiple Telomerase Components are targeted by pluripotency-associated transcription factors. Patients with dyskeratosis congenita (DC), a disorder of telomere maintenance, suffer degeneration of multiple tissues1,2,3. Patient-specific induced pluripotent stem (iPS) cells4 represent invaluable in vitro models for human degenerative disorders like DC. A cardinal feature of iPS cells is acquisition of indefinite self-renewal capacity, which is accompanied by induction of the Telomerase reverse transcriptase gene (TERT)5,6,7. We investigated whether defects in Telomerase function would limit derivation and maintenance of iPS cells from patients with DC. Here we show that reprogrammed DC cells overcome a critical limitation in Telomerase RNA Component (TERC) levels to restore telomere maintenance and self-renewal. We discovered that TERC upregulation is a feature of the pluripotent state, that several Telomerase Components are targeted by pluripotency-associated transcription factors, and that in autosomal dominant DC, transcriptional silencing accompanies a 3′ deletion at the TERC locus. Our results demonstrate that reprogramming restores telomere elongation in DC cells despite genetic lesions affecting Telomerase, and show that strategies to increase TERC expression may be therapeutically beneficial in DC patients.
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telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients
Nature, 2010Co-Authors: Suneet Agarwal, Erin M Mcloughlin, Junjiu Huang, Inhyun Park, Yuinhan LohAbstract:Patients with dyskeratosis congenita (DC), a disorder of telomere maintenance, suffer degeneration of multiple tissues. Patient-specific induced pluripotent stem (iPS) cells represent invaluable in vitro models for human degenerative disorders like DC. A cardinal feature of iPS cells is acquisition of indefinite self-renewal capacity, which is accompanied by induction of the Telomerase reverse transcriptase gene (TERT). We investigated whether defects in Telomerase function would limit derivation and maintenance of iPS cells from patients with DC. Here we show that reprogrammed DC cells overcome a critical limitation in Telomerase RNA Component (TERC) levels to restore telomere maintenance and self-renewal. We discovered that TERC upregulation is a feature of the pluripotent state, that several Telomerase Components are targeted by pluripotency-associated transcription factors, and that in autosomal dominant DC, transcriptional silencing accompanies a 3' deletion at the TERC locus. Our results demonstrate that reprogramming restores telomere elongation in DC cells despite genetic lesions affecting Telomerase, and show that strategies to increase TERC expression may be therapeutically beneficial in DC patients.
Michael Primig - One of the best experts on this subject based on the ideXlab platform.
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regulation of the conserved 3 5 exoribonuclease exosc10 rrp6 during cell division development and cancer
Biological Reviews, 2021Co-Authors: Igor Stuparevic, Ana Novacic, Rachid A Rahmouni, Anne Fernandez, Ned J C Lamb, Michael PrimigAbstract:The conserved 3'-5' exoribonuclease EXOSC10/Rrp6 processes and degrades RNA, regulates gene expression and participates in DNA double-strand break repair and control of telomere maintenance via degradation of the Telomerase RNA Component. EXOSC10/Rrp6 is part of the multimeric nuclear RNA exosome and interacts with numerous proteins. Previous clinical, genetic, biochemical and genomic studies revealed the protein's essential functions in cell division and differentiation, its RNA substrates and its relevance to autoimmune disorders and oncology. However, little is known about the regulatory mechanisms that control the transcription, translation and stability of EXOSC10/Rrp6 during cell growth, development and disease and how these mechanisms evolved from yeast to human. Herein, we provide an overview of the RNA- and protein expression profiles of EXOSC10/Rrp6 during cell division, development and nutritional stress, and we summarize interaction networks and post-translational modifications across species. Additionally, we discuss how known and predicted protein interactions and post-translational modifications influence the stability of EXOSC10/Rrp6. Finally, we explore the idea that different EXOSC10/Rrp6 alleles, which potentially alter cellular protein levels or affect protein function, might influence human development and disease progression. In this review we interpret information from the literature together with genomic data from knowledgebases to inspire future work on the regulation of this essential protein's stability in normal and malignant cells.
Justine D Miller - One of the best experts on this subject based on the ideXlab platform.
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telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients
Nature, 2010Co-Authors: Suneet Agarwal, Erin M Mcloughlin, Junjiu Huang, Inhyun Park, Justine D MillerAbstract:Patients with dyskeratosis congenita, a disorder of telomere maintenance, suffer degeneration of multiple tissues. Agarwal et al. use iPS (induced pluripotent stem) cell technology to study the mechanisms underlying the disease in humans, and in doing so they discover that reprogramming restores telomere elongation in dyskeratosis congenita cells despite genetic lesions affecting Telomerase. The reprogrammed dyskeratosis congenita cells were able to overcome a critical limitation in Telomerase RNA Component (TERC) levels to restore telomere maintenance and self-renewal, and multiple Telomerase Components are targeted by pluripotency-associated transcription factors. Strategies designed to increase TERC expression may therefore be therapeutically beneficial in dyskeratosis congenita patients. Here, iPS cell technology is used to study the mechanisms underlying dyskeratosis congenita in humans. Reprogramming restores telomere elongation in dyskeratosis congenita cells despite genetic lesions affecting Telomerase. The reprogrammed cells were able to overcome a critical limitation in Telomerase RNA Component (TERC) levels to restore telomere maintenance and self-renewal, and multiple Telomerase Components are targeted by pluripotency-associated transcription factors. Patients with dyskeratosis congenita (DC), a disorder of telomere maintenance, suffer degeneration of multiple tissues1,2,3. Patient-specific induced pluripotent stem (iPS) cells4 represent invaluable in vitro models for human degenerative disorders like DC. A cardinal feature of iPS cells is acquisition of indefinite self-renewal capacity, which is accompanied by induction of the Telomerase reverse transcriptase gene (TERT)5,6,7. We investigated whether defects in Telomerase function would limit derivation and maintenance of iPS cells from patients with DC. Here we show that reprogrammed DC cells overcome a critical limitation in Telomerase RNA Component (TERC) levels to restore telomere maintenance and self-renewal. We discovered that TERC upregulation is a feature of the pluripotent state, that several Telomerase Components are targeted by pluripotency-associated transcription factors, and that in autosomal dominant DC, transcriptional silencing accompanies a 3′ deletion at the TERC locus. Our results demonstrate that reprogramming restores telomere elongation in DC cells despite genetic lesions affecting Telomerase, and show that strategies to increase TERC expression may be therapeutically beneficial in DC patients.
Junjiu Huang - One of the best experts on this subject based on the ideXlab platform.
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telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients
Nature, 2010Co-Authors: Suneet Agarwal, Erin M Mcloughlin, Junjiu Huang, Inhyun Park, Justine D MillerAbstract:Patients with dyskeratosis congenita, a disorder of telomere maintenance, suffer degeneration of multiple tissues. Agarwal et al. use iPS (induced pluripotent stem) cell technology to study the mechanisms underlying the disease in humans, and in doing so they discover that reprogramming restores telomere elongation in dyskeratosis congenita cells despite genetic lesions affecting Telomerase. The reprogrammed dyskeratosis congenita cells were able to overcome a critical limitation in Telomerase RNA Component (TERC) levels to restore telomere maintenance and self-renewal, and multiple Telomerase Components are targeted by pluripotency-associated transcription factors. Strategies designed to increase TERC expression may therefore be therapeutically beneficial in dyskeratosis congenita patients. Here, iPS cell technology is used to study the mechanisms underlying dyskeratosis congenita in humans. Reprogramming restores telomere elongation in dyskeratosis congenita cells despite genetic lesions affecting Telomerase. The reprogrammed cells were able to overcome a critical limitation in Telomerase RNA Component (TERC) levels to restore telomere maintenance and self-renewal, and multiple Telomerase Components are targeted by pluripotency-associated transcription factors. Patients with dyskeratosis congenita (DC), a disorder of telomere maintenance, suffer degeneration of multiple tissues1,2,3. Patient-specific induced pluripotent stem (iPS) cells4 represent invaluable in vitro models for human degenerative disorders like DC. A cardinal feature of iPS cells is acquisition of indefinite self-renewal capacity, which is accompanied by induction of the Telomerase reverse transcriptase gene (TERT)5,6,7. We investigated whether defects in Telomerase function would limit derivation and maintenance of iPS cells from patients with DC. Here we show that reprogrammed DC cells overcome a critical limitation in Telomerase RNA Component (TERC) levels to restore telomere maintenance and self-renewal. We discovered that TERC upregulation is a feature of the pluripotent state, that several Telomerase Components are targeted by pluripotency-associated transcription factors, and that in autosomal dominant DC, transcriptional silencing accompanies a 3′ deletion at the TERC locus. Our results demonstrate that reprogramming restores telomere elongation in DC cells despite genetic lesions affecting Telomerase, and show that strategies to increase TERC expression may be therapeutically beneficial in DC patients.
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telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients
Nature, 2010Co-Authors: Suneet Agarwal, Erin M Mcloughlin, Junjiu Huang, Inhyun Park, Yuinhan LohAbstract:Patients with dyskeratosis congenita (DC), a disorder of telomere maintenance, suffer degeneration of multiple tissues. Patient-specific induced pluripotent stem (iPS) cells represent invaluable in vitro models for human degenerative disorders like DC. A cardinal feature of iPS cells is acquisition of indefinite self-renewal capacity, which is accompanied by induction of the Telomerase reverse transcriptase gene (TERT). We investigated whether defects in Telomerase function would limit derivation and maintenance of iPS cells from patients with DC. Here we show that reprogrammed DC cells overcome a critical limitation in Telomerase RNA Component (TERC) levels to restore telomere maintenance and self-renewal. We discovered that TERC upregulation is a feature of the pluripotent state, that several Telomerase Components are targeted by pluripotency-associated transcription factors, and that in autosomal dominant DC, transcriptional silencing accompanies a 3' deletion at the TERC locus. Our results demonstrate that reprogramming restores telomere elongation in DC cells despite genetic lesions affecting Telomerase, and show that strategies to increase TERC expression may be therapeutically beneficial in DC patients.
