| 27103453 | Telomerase is composed of the catalytic subunit TERT (Telomerase reverse transcriptase),RNA subunit TERC (Telomerase RNA component) and other telomerase associated proteins |
| 27103453 | Trafficking and assemble of TERT and TERC, as well as recruitment to telomeres, are also involved in this process |
| 26571381 | GSE4 expression also activated c-myc and TERT promoters and increase of c-myc, TERT and TERC expression |
| 26571381 | Mutation of the Aspartic Acid residue that is conserved in the pseudouridine synthase domain present in GSE4 did not impair its activity, except for the repression of c-myc promoter activity and the decrease of c-myc, TERT and TERC gene expression in dyskerin-mutated cells |
| 26518879 | Mutations of human telomerase RNA component (TERC) and telomerase reverse transcriptase (TERT) are associated with a subset of lung aging diseases, but the mechanisms by which TERC and TERT participate in lung diseases remain unclear |
| 26518879 | In this report, we show that knock-out (KO) of the mouse gene Terc or Tert causes pulmonary alveolar stem cell replicative senescence, epithelial impairment, formation of alveolar sacs, and characteristic inflammatory phenotype |
| 26386121 | Moreover, telomere-associated foci predict age-dependent emphysema, and late-generation Terc null mice, which harbor dysfunctional telomeres, show early-onset emphysema |
| 26277387 | We investigated kidneys from young and old Terc(+/+) and Terc(-/-) mice of early (G1) and late (G4, G5) generations |
| 26277387 | Functional parameters declined and age-related morphological changes increased in late generation Terc(-/-) mice and with further age |
| 26277387 | Podocyte loss was only seen in old G4 Terc(-/-) |
| 26277387 | Whereas p21(CIP1/WAF1) was highest in old G1 and G4 Terc(-/-), telomere shortening and p16(INK4a) expression, also significantly associated with later generation young Terc(-/-), were not further induced in old Terc(-/-) mice |
| 26277387 | Both, young and old late generation Terc(-/-), showed increased pro-inflammatory cytokine levels |
| 26277387 | Young late generation Terc(-/-) animals show mild functional and histological abnormalities, the presence of cellular senescence explains their kidneys' limited regenerative capacity |
| 26277387 | While these aspects resemble the situation seen in aged human kidneys, the lack of telomere shortening and p16(INK4a) induction in older Terc(-/-) animals differs from observations in old human kidneys and may result from clearance of senescent cells |
| 25892207 | We investigated the effect of cellular aging induced by telomere shortening on microglia by the use of mice lacking the telomerase RNA component (TERC) and design-based stereology |
| 25892207 | TERC knockout (KO) mice had a significantly reduced number of CD11b(+) microglia in the dentate gyrus |
| 25892207 | Microglia in TERC KO mice maintained a homogenous distribution and normal expression of CD45 and CD68 and the aging marker, ferritin, but were morphologically distinct from microglia in both adult and old wild-type mice |
| 25892207 | TERC KO mice also showed increased cellular apoptosis and impaired spatial learning |
| 25760322 | Aging is associated with telomere shortening, and both telomerase reverse transcriptase (TerT) and RNA (TerC) are essential to maintain telomere length |
| 25760322 | To define a role of telomerase deficiency in susceptibility to AKI, we used ischemia/reperfusion injury in wild-type mice or mice with either TerC or TerT deletion |
| 25760322 | However, either TerC or TerT knockout significantly delayed recovery compared with wild-type mice |
| 25760322 | Electron microscopy showed increased autophagosome formation in renal tubular epithelial cells in wild-type mice but a significant delay of their development in TerC and TerT knockout mice |
| 25735595 | To reflect telomere shortening in human aging, we investigated aortas from telomerase deficient (Terc(-/-)) mice of generation 3 (G3) |
| 25735595 | Endothelium-dependent vasodilation in aged wildtype and in Terc(-/-) G3 mice was impaired |
| 25735595 | A combination of the superoxide dismutase mimetic 1-Oxyl-2,2,6, 6-tetramethyl-4-hydroxypiperidine (TEMPOL) and the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor apocynin significantly improved endothelium-dependent vasodilation in aged wildtype and Terc(-/-) G3 mice compared to untreated controls |
| 25142166 | In contrast, the expression level of RNA component TERC did not altered |
| 24626990 | We evaluated the skeletal phenotypes of mice with disrupted telomere maintenance mechanisms as models for human bone aging, including mutants in Werner helicase (Wrn(-/-)), telomerase (Terc(-/-)) and Wrn(-/-)Terc(-/-) double mutants |
| 24626990 | Compared with young wild-type (WT) mice, micro-computerized tomography analysis revealed that young Terc(-/-) and Wrn(-/-)Terc(-/-) mice have decreased trabecular bone volume, trabecular number and trabecular thickness, as well as increased trabecular spacing |
| 24626990 | In cortical bone, young Terc(-/-) and Wrn(-/-)Terc(-/-) mice have increased cortical thinning, and increased porosity relative to age-matched WT mice |
| 24626990 | These trabecular and cortical changes were accelerated with age in Terc(-/-) and Wrn(-/-)Terc(-/-) mice compared with older WT mice |
| 24626990 | Histological quantification of osteoblasts in aged mice showed a similar number of osteoblasts in all genotypes; however, significant decreases in osteoid, mineralization surface, mineral apposition rate and bone formation rate in older Terc(-/-) and Wrn(-/-)Terc(-/-) bone suggest that osteoblast dysfunction is a prominent feature of precocious aging in these mice |
| 24626990 | Significant alterations in mechanical parameters (structure model index, degree of anistrophy and moment of inertia) of the Terc(-/-) and Wrn(-/-)Terc(-/-) femurs compared with WT mice were also observed |
| 24626990 | Taken together, our results suggest that Terc(-/-) and Wrn(-/-)Terc(-/-) mutants recapitulate the human bone aging phenotype and are useful models for studying age-related osteoporosis |
| 24478790 | Many studies have shown that leukocyte telomere length is a heritable trait, and several candidate genes have been identified, including TERT, TERC, OBFC1, and CTC1 |
| 23268535 | These four genes encode two surfactant proteins, surfactant protein C (encoded by SFTPC) and surfactant protein A2 (SFTPA2), and two components of the telomerase complex, telomerase reverse transcriptase (TERT) and the RNA component of telomerase (TERC) |
| 23019197 | In this study, we compared basal and stimulated gastric acid and duodenal HCO(3)(-) secretory rates in aged late-generation (G(3)) telomerase-deficient (mTERC(-/-)) mice, which are characterized by severe telomere dysfunction due to the inability to elongate telomeres during cell division |
| 23019197 | We found that basal and forskolin-stimulated HCO(3)(-) secretion and short-circuit current (I(sc)) in isolated duodenal mucosa of G(3) mTERC(-/-) mice were markedly reduced compared with age-matched wild-type mice |
| 23019197 | In contrast, basal and forskolin-stimulated acid secretory rates in isolated G(3) mTERC(-/-) gastric mucosa were not significantly altered |
| 23019197 | Correspondingly, duodenal mucosa of G(3) mTERC(-/-) mice showed slimming and shortening of villi, whereas gastric mucosal histology was not significantly altered |
| 23019197 | The further knockout of p21, which is a downstream effector of telomere shortening-induced senescence, rescued villus atrophy of duodenal mucosa, and basal and forskolin-stimulated duodenal HCO(3)(-) secretion and I(sc) in mTERC(-/-) p21(-/-) double-knockout mice were not different from wild-type controls |
| 22973556 | The human holoenzyme telomerase is a ribonucleoprotein composed by a catalytic subunit, hTERT, an RNA component, hTR, and a group of associated proteins |
| 22882466 | The phenotype was aggravated in brains of late-generation TERC-/- mice with dysfunctional telomeres |
| 22847419 | Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) induces cancer cell senescence by interacting with telomerase RNA component |
| 22847419 | We report here that GAPDH interacts with the telomerase RNA component (TERC), inhibits telomerase activity, and induces telomere shortening and breast cancer cell senescence |
| 22847419 | The Rossmann fold containing NAD(+) binding region on GAPDH is responsible for the interaction with TERC, whereas a lysine residue in the GAPDH catalytic domain is required for inhibiting telomerase activity and disrupting telomere maintenance |
| 22843416 | Interestingly, the expression of hTR in hiPSC-derived CMs was not significantly downregulated, unlike in hESC-derived CMs |
| 22661914 | Heterozygous carriers for mutations in either the telomerase reverse transcriptase (hTERT) or the telomerase RNA template (hTERC) gene displayed striking and comparable telomere length deficits |
| 22621437 | Using mouse models of disrupted telomere maintenance molecules, including mutants in the Werner helicase (Wrn(-/-) ), telomerase (Terc(-/-) ), and Wrn(-/-) Terc(-/-) double mutants predisposed to accelerated bone loss, we measured telomere dysfunction-induced foci (TIFs) and markers of osteoblast differentiation in mesenchymal progenitor cells (MPCs) |
| 22110763 | Here, we analyzed the influence of telomere shortening (a basic mechanism of cellular aging) on homeostasis and regenerative reserve in response to chemical induced injury of the OE in late generation telomere knockout mice (G3 mTerc(-/-)) with short telomeres compared to wild type mice (mTerc(+/+)) with long telomeres |
| 22110763 | In contrast, the regenerative response to chemical induced injury of the OE was significantly impaired in G3 mTerc(-/-) mice compared to mTerc(+/+) mice |
| 22110763 | Seven days after chemical induced damage, G3 mTerc(-/-) mice exhibited significantly enlarged areas of persisting atrophy compared to mTerc(+/+) mice (p = 0 |
| 21708826 | TERC polymorphisms are associated both with susceptibility to colorectal cancer and with longer telomeres |
| 21708826 | RESULTS: Carriers of the common allele at SNP rs10936599, near the telomerase RNA component (TERC) locus, had significantly longer telomeres |
| 21708826 | In silico analysis showed that SNP rs2293607 was strongly correlated with rs10936599, mapped within TERC transcripts, had a predicted effect on messenger RNA folding and lay at a reported transcription factor binding site |
| 21708826 | TERC mRNA were expressed, differing only at the alleles of rs2293607, in CRC cell line HCT116 |
| 21708826 | The long-telomere/CRC-risk allele was associated with higher levels of TERC mRNA and the formation of longer telomeres |
| 21708826 | CONCLUSIONS: Common genetic variation at TERC is associated with both longer telomeres and an increased risk of CRC, a potential mechanism being reduced levels of cell senescence or death |
| 21693539 | I3C strongly downregulated transcript expression of the catalytic subunit of the human telomerase (hTERT) gene, which correlated with the dose-dependent indole-mediated G(1) cell cycle arrest without altering the transcript levels of the RNA template (hTR) for telomerase elongation |
| 20195488 | We therefore have analysed whether an increase in mitochondrial derived oxidative stress in response to heterozygous deletion of superoxide dismutase (Sod2(+/-)) would exacerbate aging phenotypes in telomere dysfunctional (mTerc(-/-)) mice |
| 20195488 | Moreover, heterozygous deletion of Sod2 did not accelerate the depletion of stem cells and the impairment in organ maintenance in aging mTerc(-/-) mice |
| 20195488 | In agreement with these observations, Sod2 haploinsufficiency did not lead to a further reduction in lifespan of mTerc(-/-) mice |
| 18454043 | Compounds inhibiting the RNA component of telomerase, hTERC, include peptide nucleic acids, 2-5A antisense oligonucleotides, and N3'-P5' thio-phosphoramidates |
| 18157152 | Here we report the identification and functional characterization of TER1, the telomerase RNA component from fission yeast Schizosaccharomyces pombe |
| 17634580 | Telomerase is a ribonucleoprotein complex composed minimally of telomere reverse transcriptase gene (hTERT) and RNA template (hTR), and its enzyme activity in cells is primarily limited by the level of hTERT expression |
| 17396137 | We used the p53 ( R172P ) knock-in mouse, which is unable to induce apoptosis but retains intact cell-cycle arrest and cellular senescence pathways, to show that spontaneous tumorigenesis is potently repressed in Terc -/- p53 ( R172P ) mice |
| 17314245 | Recent genetic evidence from the mTerc(-/-) Wrn(-/-) mouse demonstrates that mice with critically shortened telomeres display aging phenotypes reminiscent of human WS, further reinforcing the notion that telomere dysfunction is required for the manifestation of aging pathophysiologies in the setting of WRN deficiency |
| 17175117 | A specific telomerase inhibitor, GRN163L that is complementary to the template region of the telomerase ribonucleic acid component (hTR) |
| 16435298 | Telomerase RNA component (TERC) and telomerase reverse transcriptase (TERT) function together to elongate telomeres and to protect chromosomal ends |
| 16435298 | 1,2 This telomerase functional characteristic is TERC independent and is operated through a mechanism other than telomere elongation |
| 16308915 | The current studies were designed to characterize the accelerated senescence response to radiation in the breast tumour cell in terms of its dependence on functional p53 and its relationship to telomerase activity, telomere lengths, expression of human telomerase reverse transcriptase (hTERT, the catalytic subunit of telomerase) and human telomerase RNA (hTR, the RNA subunit of telomerase), as well as the induction of cytogenetic aberrations |
| 16308915 | Radiation did not suppress expression of either hTERT or hTR, alter telomerase activity or induce telomere shortening |
| 16308915 | Accelerated senescence in response to ionizing radiation is p53 dependent and associated with telomer dysfunction but is unrelated to changes in telomerase activity or telomere lengths, expression of hTERT and hTR |
| 15326392 | Telomerase, whose core components are a reverse transcriptase (TERT) and an integral RNA (TERC) maintains telomere ends |
| 15326392 | Heterozygous TERC mutations in man have been shown to underlie the rare inherited skin and bone marrow failure condition dyskeratosis congenita and a number of patients initially classified as idiopathic aplastic anemia have also been found to be mutated in one allele of the TERC gene |
| 15326392 | Families in which TERC mutations are segregating show disease anticipation, the severity of the disease increasing in successive generations due to decreasing telomere length |
| 15326392 | These data, along with biochemical analysis of mutated Terc and studies of Terc deficient mice show that in man and mouse haploinsufficiency for TERC leads to inability to correctly maintain telomeres, and highlights the importance of finely controlled telomerase levels in striking a balance between the processes of aging and cancer |
| 12873987 | GRN163 was competitive with telomeric primer binding, primarily because of hybridization to human telomerase RNA (hTR) component |
| 12135464 | Human telomerase RNA component expression in Spitz nevi, common melanocytic nevi, and malignant melanomas |
| 12018844 | In contrast, expression levels of human telomerase RNA (hTR) were identical in both MKN/ADR and MKN-45 cell lines |
| 11925625 | Expressions of subunits of telomerase, hTR and hTERT, were assessed by RT-PCR |
| 11850790 | These oligonucleotides are complementary to the template region of the RNA domain of telomerase (hTR) |
| 11850790 | 5 microM of FuGENE6 formulated 13-mer thio-phosphoramidates, fully complementary to hTR, resulted in gradual telomere shortening, followed by cellular senescence and apoptosis, as would be predicted for a telomerase inhibitor |
| 11531263 | Recently, a number of relevant genes have been cloned, including these encoding three major components of human telomerase: human telomerase RNA component (hTR), human telomerase reverse transcriptase (hTERT), and telomerase-associated protein-1 (TEP1) |
| 11481865 | They included those for human telomerase RNA component (hTR), human telomerase reverse transcriptase (hTERT), and telomerase-associated protein 1 (TEP1) |
| 11123427 | Recently several relevant genes have been cloned, including those encoding three major components of human telomerase: human telomerase RNA component (hTR), human telomerase reverse transcriptase (hTERT), and telomerase-associated protein-1 (TEP1) |
| 11123427 | In all 10 malignant cell lines with telomerase activity, hTR, hTERT mRNA, and TEP1 mRNA were expressed, while in normal monocytes and granulocytes without telomerase activity, expression of hTR, but not hTERT mRNA was detected |
| 11071470 | The aim of this study was to measure quantitatively the telomerase activity and human telomerase RNA component (hTR) content in gastric cancer and to examine the relation between these values and histologic factors including Helicobacter pylori as a risk factor for gastric cancer |
| 11071470 | Telomerase activity was measured by a modified telomeric repeat amplification protocol in cancerous and noncancerous tissues (intestinal metaplasia, chronic gastritis, normal mucosa) from 27 gastric cancer patients; hTR expression was examined by the quantitative reverse transcriptase-polymerase chain reaction using fluorescent probes |
| 10049783 | The majority of gastric cancers express high levels of human telomerase template RNA (hTR) that is essential for cellular survival |
| 10049783 | In this study, we examined whether antisense hTR (ahTR) had a growth inhibitory effect on three gastric cancer cell lines, MKN-1, MKN-28, and TMK-1, through transfection via an ahTR expression vector |
| 9613109 | By introducing antisense hTR expression construct into tumor cells, reduction of telomeric DNAs and crisis or cellular senescence occurred in several human cancer cell lines |
| 9613109 | Antisense oligonucleotides to hTR synthesized with peptide nucleic acids and phosphorothioate deoxyribonucleic acids(PS) also inhibited telomerase activity in vitro |
| 9613109 | Furthermore, PS antisense hTR had significant effect to decrease tumor size and a number of metastatic nodules in a xenograft human cancer-nude mouse model |
| 9613109 | Taken together, the telomerase inhibitors targeting to hTR are expected to be novel anti-tumor agents |
| 9546436 | We have therefore cloned the promoter regions of the human (hTR), and mouse, (terc), telomerase RNA genes in order to identify the regulatory elements controlling telomerase RNA gene transcription |
| 9546436 | 76 kb encompassing the hTR gene promoter region was sequenced, as was 4 kb encompassing the terc promoter |
| 9398860 | Reconstitution of human telomerase with the template RNA component hTR and the catalytic protein subunit hTRT |
| 9398860 | In addition to the human telomerase RNA component (hTR; ref |
| 9398860 | We now report that in vitro transcription and translation of hTRT when co-synthesized or mixed with hTR reconstitutes telomerase activity that exhibits enzymatic properties like those of the native enzyme |
| 9343401 | Expression of mutant hTR resulted in the appearance of mutant telomerase activity and in the synthesis of mutant telomeres |
| 9175740 | That this is not the mechanism of the abnormally long telomeres in ALT cell lines was demonstrated by the finding that seven of seven ALT lines have wild-type human telomerase RNA (hTR) sequence, including a novel polymorphism that is present in 30% of normal individuals |
| 9175740 | We found that two ALT cell lines have no detectable expression of the hTR gene |
| 9175740 | This shows that the ALT mechanism in these cell lines is not dependent on hTR |
| 9175740 | Expression of exogenous hTR via infection of these cells with a recombinant hTR-adenovirus vector did not result in telomerase activity, indicating that their lack of telomerase activity is not due to absence of hTR expression |
| 9175740 | We conclude that the ALT mechanism is not dependent on the expression of hTR, and does not involve mutations in the hTR sequence |
| 9524757 | We studied telomerase activity and expression of the mouse telomerase RNA component (mTR) in two different transgenic mouse models of multistage tumorigenesis: models of islet cell carcinoma and squamous cell carcinoma |
