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Telomere reverse transcriptase

Diqi Yang, Lei Wang, Pengfei Lin, Tingting Jiang, Nan Wang, Fan Zhao, Huatao Chen, Keqiong Tang, Dong Zhou, Aihua Wang, Yaping Jin
With granulosa and theca cells, the ovaries are responsible for producing oocytes and secreting sex steroids such as estrogen and progesterone. Endoplasmic reticulum stress (ERS) plays an important role in follicle atresia and embryo implantation. In this study, goat granulosa cells were isolated from medium-sized (4-6 mm) healthy follicles. Primary granulosa cells were immortalized by transfection with human telomerase reverse transcriptase (hTERT) to establish a goat granulosa cell line (hTERT-GGCs). These hTERT-GGCs expressed hTERT and had relatively long telomeres at passage 50...
October 15, 2016: Journal of Reproduction and Development
Rajendra Kumar Agrawal, Hong-Wei Wang, Marlene Belfort
Group II introns are large catalytic RNAs that form a ribonucleoprotein (RNP) complex by binding to an intron-encoded protein (IEP). The IEP, which facilitates both RNA splicing and intron mobility, has multiple activities including reverse transcriptase. Recent structures of a group II intron RNP complex and of IEPs from diverse bacteria fuel arguments that group II introns are ancestrally related to eukaryotic spliceosomes as well as to telomerase and viruses. Furthermore, recent structural studies of various functional states of the spliceosome allow us to draw parallels between the group II intron RNP and the spliceosome...
October 11, 2016: RNA Biology
Lucy Cassar, Craig Nicholls, Alex R Pinto, Ruping Chen, Lihui Wang, He Li, Jun-Ping Liu
Human telomerase reverse transcriptase (hTERT) plays a central role in telomere lengthening for continuous cell proliferation, but it remains unclear how extracellular cues regulate telomerase lengthening of telomeres. Here we report that the cytokine bone morphogenetic protein-7 (BMP7) induces the hTERT gene repression in a BMPRII receptor- and Smad3-dependent manner in human breast cancer cells. Chonic exposure of human breast cancer cells to BMP7 results in short telomeres, cell senescence and apoptosis...
September 30, 2016: Protein & Cell
Marta Viana-Pereira, Gisele Caravina Almeida, João Norberto Stavale, Susana Malheiro, Carlos Clara, Patrícia Lobo, José Pimentel, Rui Manuel Reis
Hotspot activating mutations of the telomerase reverse transcriptase (hTERT) promoter region were recently described in several tumor types. These mutations lead to enhanced expression of telomerase, being responsible for telomere maintenance and allowing continuous cell division. Additionally, there are alternative telomere maintenance mechanisms, associated with histone H3 mutations, responsible for disrupting the histone code and affecting the regulation of transcription. Here, we investigated the clinical relevance of these mechanistically related molecules in medulloblastoma...
October 1, 2016: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
Aristomenis Thanos, Bozho Todorich, Stephen M Hypes, Yoshihiro Yonekawa, Benjamin Thomas, Sandeep Randhawa, Kimberly A Drenser, Michael T Trese
PURPOSE: To report a novel presentation of dyskeratosis congenita masquerading as familial exudative vitreoretinopathy. METHODS: Observational case series involving single family and literature review. RESULTS: A brother and sister were diagnosed with familial exudative vitreoretinopathy at ages 4 and 2, respectively. Both patients were managed with laser photocoagulation. Eight years after the initial presentation, both siblings developed pancytopenia secondary to bone marrow failure...
September 28, 2016: Retinal Cases & Brief Reports
Eunju Im, Jong Bok Yoon, Han-Woong Lee, Kwang Chul Chung
Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of telomerase, an RNA-dependent DNA polymerase that elongates telomeric DNA. hTERT displays several extra-telomeric functions that are independent of its telomere-regulatory function, including tumor progression and neuronal cell death regulation. In this study, we evaluated these additional hTERT non-telomeric functions. We determined that hTERT interacts with several 19S and 20S proteasome subunits. The 19S regulatory particle and 20S core particle are part of 26S proteasome complex, which plays a central role in ubiquitin-dependent proteolysis...
September 20, 2016: Journal of Cellular Physiology
Hyun-Jin Kang, Yunxi Cui, Holly Yin, Amy Scheid, William P D Hendricks, Jessica Schmidt, Aleksandar Sekulic, Deming Kong, Jeffrey M Trent, Vijay Gokhale, Hanbin Mao, Laurence H Hurley
Activation of human telomerase reverse transcriptase (hTERT) is necessary for limitless replication in tumorigenesis. Whereas hTERT is transcriptionally silenced in normal cells, most tumor cells reactivate hTERT expression by alleviating transcriptional repression through diverse genetic and epigenetic mechanisms. Transcription-activating hTERT promoter mutations have been found to occur at high frequencies in multiple cancer types. These mutations have been shown to form new transcription factor binding sites that drive hTERT expression, but this model cannot fully account for differences in wild-type (WT) and mutant promoter activation and has not yet enabled a selective therapeutic strategy...
October 5, 2016: Journal of the American Chemical Society
Ekta Khattar, Pavanish Kumar, Chia Yi Liu, Semih Can Akıncılar, Anandhkumar Raju, Manikandan Lakshmanan, Julien Jean Pierre Maury, Yu Qiang, Shang Li, Ern Yu Tan, Kam M Hui, Ming Shi, Yuin Han Loh, Vinay Tergaonkar
Transcriptional reactivation of telomerase reverse transcriptase (TERT) reconstitutes telomerase activity in the majority of human cancers. Here, we found that ectopic TERT expression increases cell proliferation, while acute reductions in TERT levels lead to a dramatic loss of proliferation without any change in telomere length, suggesting that the effects of TERT could be telomere independent. We observed that TERT determines the growth rate of cancer cells by directly regulating global protein synthesis independently of its catalytic activity...
October 3, 2016: Journal of Clinical Investigation
Muhamed Baljevic, Bogdan Dumitriu, Ju-Whei Lee, Elisabeth M Paietta, Peter H Wiernik, Janis Racevskis, Christina Chen, Eytan M Stein, Robert E Gallagher, Jacob M Rowe, Frederick R Appelbaum, Bayard L Powell, Richard A Larson, Steven E Coutré, Jeffrey Lancet, Mark R Litzow, Selina M Luger, Neal S Young, Martin S Tallman
Telomeres are the capping ends of chromosomes that protect the loss of genetic material and prevent chromosomal instability. In human tissue-specific stem/progenitor cells, telomere length (TL) is maintained by the telomerase complex, which consists of a reverse transcriptase catalytic subunit (TERT) and an RNA template (TERC). Very short telomeres and loss-of-function mutations in the TERT and TERC genes have been reported in acute myeloid leukemia, but the role of telomeres in acute promyelocytic leukemia (APL) has not been well established...
September 16, 2016: Acta Haematologica
Martha L Slattery, Jennifer S Herrick, Andrew J Pellatt, Roger K Wolff, Lila E Mullany
It has been proposed that miRNAs are involved in the control of telomeres. We test that hypothesis by examining the association between miRNAs and telomere length (TL). Additionally, we evaluate if genetic variation in telomerase reverse transcriptase (TERT) is associated with miRNA expression levels. We use data from a population-based study of colorectal cancer (CRC), where we have previously shown associations between TL and TERT and CRC, to test associations between TL and miRNA expression and TERT and miRNA expression...
2016: PloS One
Joana Ropio, Jean-Philippe Merlio, Paula Soares, Edith Chevret
Telomerase expression and telomere maintenance are critical for cell proliferation and survival, and they play important roles in development and cancer, including hematological malignancies. Transcriptional regulation of the rate-limiting subunit of human telomerase reverse transcriptase gen (hTERT) is a complex process, and unveiling the mechanisms behind its reactivation is an important step for the development of diagnostic and therapeutic applications. Here, we review the main mechanisms of telomerase activation and the associated hematologic malignancies...
2016: Genes
Omamuyovwi M Ijomone, Mahfuzur R Miah, Tanara V Peres, Polycarp U Nwoha, Michael Aschner
Exposure to manganese (Mn) represents an environmental risk factor for Parkinson's disease (PD). Recent evidence suggests that telomerase reverse transcriptase (TERT), the catalytic subunit of mammalian telomerase participates in non-telomeric functions and may play a role in cellular protection from oxidative stress and DNA damage. trt-1 is the catalytic subunit of telomerase in Caenorhabditis elegans (C. elegans). The present study investigated the relationship between trt-1 mutation and Mn-induced neurotoxicity...
September 1, 2016: Neurotoxicology
Brooke R Druliner, Xiaoyang Ruan, Ruth Johnson, Diane Grill, Daniel O'Brien, Tsung-Po Lai, Shahrooz Rashtak, Donna Felmlee-Devine, Jill Washechek-Aletto, Andrei Malykh, Thomas Smyrk, Ann Oberg, Hongfang Liu, Jerry W Shay, David A Ahlquist, Lisa A Boardman
OBJECTIVE: Whereas few adenomas become cancer, most colorectal cancers arise from adenomas. Telomere length is a recognized biomarker in multiple cancers, and telomere maintenance mechanisms (TMM) are exploited by malignant cells. We sought to determine whether telomere length and TMM distinguish cancer-associated adenomas from those that are cancer-free. METHODS: Tissues were identified as cancer-adjacent polyp (CAP)-residual adenoma contiguous with cancer-and cancer-free polyp (CFP)-adenomas without malignancy...
2016: Clinical and Translational Gastroenterology
HuyTram N Nguyen, Amy Lie, Tie Li, Reshmi Chowdhury, Fei Liu, Byram Ozer, Bowen Wei, Richard M Green, Benjamin M Ellingson, He-Jing Wang, Robert Elashoff, Linda M Liau, William H Yong, Phioanh L Nghiemphu, Timothy Cloughesy, Albert Lai
BACKGROUND: Promoter mutation in the human telomerase reverse transcriptase gene (hTERT) occurs in ~75% of primary glioblastoma (GBM). Although the mutation appears to upregulate telomerase expression and contributes to the maintenance of telomere length, its clinical significance remains unclear. METHODS: We performed hTERT promoter genotyping on 303 isocitrate dehydrogenase 1 wild-type GBM tumors treated with standard chemoradiotherapy. We also stratified 190 GBM patients from the database of The Cancer Genome Atlas (TCGA) by hTERT gene expression...
August 29, 2016: Neuro-oncology
Vivian Francília Silva Kahl, Juliana da Silva, Fernanda Rabaioli da Silva
Various pesticides in the form of mixtures must be used to keep tobacco crops pest-free. Recent studies have shown a link between occupational exposure to pesticides in tobacco crops and increased damage to the DNA, mononuclei, nuclear buds and binucleated cells in buccal cells as well as micronuclei in lymphocytes. Furthermore, pesticides used specifically for tobacco crops shorten telomere length (TL) significantly. However, the molecular mechanism of pesticide action on telomere length is not fully understood...
September 2016: Mutation Research
Armita Bahrami, Seungjae Lee, Inga-Marie Schaefer, Jennifer M Boland, Kurt T Patton, Stanley Pounds, Christopher D Fletcher
Solitary fibrous tumor is a mesenchymal neoplasm exhibiting a broad spectrum of biological behavior and harboring the NAB2-STAT6 fusion. Clinicopathologic parameters are currently used in risk-prediction models for solitary fibrous tumor, but the molecular determinants of malignancy in solitary fibrous tumors remain unknown. We proposed that the activation of telomere maintenance pathways confers a perpetual malignant phenotype to these tumors. Therefore, we investigated telomerase reverse transcriptase (TERT) reactivation induced by promoter mutations as a potential molecular mechanism for aggressive clinical behavior in solitary fibrous tumor...
August 26, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Muhammad Khairul Ramlee, Jing Wang, Wei Xun Toh, Shang Li
Embryonic stem cells and induced pluripotent stem cells have the ability to maintain their telomere length via expression of an enzymatic complex called telomerase. Similarly, more than 85%-90% of cancer cells are found to upregulate the expression of telomerase, conferring them with the potential to proliferate indefinitely. Telomerase Reverse Transcriptase (TERT), the catalytic subunit of telomerase holoenzyme, is the rate-limiting factor in reconstituting telomerase activity in vivo. To date, the expression and function of the human Telomerase Reverse Transcriptase (hTERT) gene are known to be regulated at various molecular levels (including genetic, mRNA, protein and subcellular localization) by a number of diverse factors...
2016: Genes
Muhammad Ali, Sushil Devkota, Jae-Il Roh, Jaehoon Lee, Han-Woong Lee
Telomerase is a reverse transcriptase that consists of the telomerase RNA component (TERC) and the reverse transcriptase catalytic subunit (TERT) and specializes in the elongation of telomere ends. New evidence suggests that beyond classical telomere maintenance, TERT also possesses telomere length-independent functions that are executed via interaction with other binding proteins. One such reported TERT-interacting proteins is mTOR, a master nutrient sensor that is upregulated in several cancers; however, the physiological implications of the TERT-mTOR interaction in normal cellular processes as well as in tumorigenesis are poorly understood...
September 23, 2016: Biochemical and Biophysical Research Communications
Chad A Newton, Kiran Batra, Jose Torrealba, Julia Kozlitina, Craig S Glazer, Carlos Aravena, Keith Meyer, Ganesh Raghu, Harold R Collard, Christine Kim Garcia
Heterozygous mutations in four telomere-related genes have been linked to pulmonary fibrosis, but little is known about similarities or differences of affected individuals.115 patients with mutations in telomerase reverse transcriptase (TERT) (n=75), telomerase RNA component (TERC) (n=7), regulator of telomere elongation helicase 1 (RTEL1) (n=14) and poly(A)-specific ribonuclease (PARN) (n=19) were identified and clinical data were analysed.Approximately one-half (46%) had a multidisciplinary diagnosis of idiopathic pulmonary fibrosis (IPF); others had unclassifiable lung fibrosis (20%), chronic hypersensitivity pneumonitis (12%), pleuroparenchymal fibroelastosis (10%), interstitial pneumonia with autoimmune features (7%), an idiopathic interstitial pneumonia (4%) and connective tissue disease-related interstitial fibrosis (3%)...
August 18, 2016: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Theresa Kreilmeier, Doris Mejri, Marlene Hauck, Miriam Kleiter, Klaus Holzmann
Long non-coding transcripts from telomeres, called telomeric repeat-containing RNA (TERRA), were identified as blocking telomerase activity (TA), a telomere maintenance mechanism (TMM), in tumors. We expressed recombinant TERRA transcripts in tumor cell lines with TA and with alternative lengthening of telomeres (ALT) to study effects on TMM and cell growth. Adeno- and lentivirus constructs (AV and LV) were established for transient and stable expression of approximately 130 units of telomere hexanucleotide repeats under control of cytomegalovirus (CMV) and human RNase P RNA H1 (hH1) promoters with and without polyadenylation, respectively...
2016: Genes
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