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Science 1 September 1995:
Vol. 269. no. 5228, pp. 1236 - 1241
DOI: 10.1126/science.7544491
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Articles

Science, Vol 269, Issue 5228, 1236-1241
Copyright © 1995 by American Association for the Advancement of Science

articles

The RNA component of human telomerase

J Feng, WD Funk, SS Wang, SL Weinrich, AA Avilion, CP Chiu, RR Adams, E Chang, RC Allsopp, J Yu, and al. et

Geron Corporation, Menlo Park, CA 94025, USA.

Eukaryotic chromosomes are capped with repetitive telomere sequences that protect the ends from damage and rearrangements. Telomere repeats are synthesized by telomerase, a ribonucleic acid (RNA)-protein complex. Here, the cloning of the RNA component of human telomerase, termed hTR, is described. The template region of hTR encompasses 11 nucleotides (5'-CUAACCCUAAC) complementary to the human telomere sequence (TTAGGG)n. Germline tissues and tumor cell lines expressed more hTR than normal somatic cells and tissues, which have no detectable telomerase activity. Human cell lines that expressed hTR mutated in the template region generated the predicted mutant telomerase activity. HeLa cells transfected with an antisense hTR lost telomeric DNA and began to die after 23 to 26 doublings. Thus, human telomerase is a critical enzyme for the long-term proliferation of immortal tumor cells.


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Telomerase Regulation of Myofibroblast Differentiation.
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J. Nucl. Med. 47, 270-277
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J. Virol. 80, 281-295
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Expression and Suppression of Human Telomerase RNA.
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N. Zhao, G. Huang, L. Guo, and S.-H. Lu (2006)
Experimental Biology and Medicine 231, 84-90
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Abundant novel transcriptional units and unconventional gene pairs on human chromosome 22.
L. Lipovich and M.-C. King (2006)
Genome Res. 16, 45-54
   Abstract »    Full Text »    PDF »
High Telomerase RNA Expression Level Is an Adverse Prognostic Factor for Favorable-Histology Wilms' Tumor.
J. S. Dome, C. A. Bockhold, S. M. Li, S. D. Baker, D. M. Green, E. J. Perlman, D. A. Hill, and N. E. Breslow (2005)
J. Clin. Oncol. 23, 9138-9145
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T. Racek, N. Mise, Z. Li, A. Stoll, and B. M. Putzer (2005)
J. Biol. Chem. 280, 40402-40405
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CTCF binds the proximal exonic region of hTERT and inhibits its transcription.
S. Renaud, D. Loukinov, F. T. Bosman, V. Lobanenkov, and J. Benhattar (2005)
Nucleic Acids Res. 33, 6850-6860
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The effect of TERC haploinsufficiency on the inheritance of telomere length.
F. Goldman, R. Bouarich, S. Kulkarni, S. Freeman, H.-Y. Du, L. Harrington, P. J. Mason, A. Londono-Vallejo, and M. Bessler (2005)
PNAS 102, 17119-17124
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J Natl Cancer Inst 97, 1589-1600
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Dissociation of telomerase activity and telomere length maintenance in primitive human hematopoietic cells.
J. C. Y. Wang, J. K. Warner, N. Erdmann, P. M. Lansdorp, L. Harrington, and J. E. Dick (2005)
PNAS 102, 14398-14403
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H. Kanao, T. Enomoto, T. Kimura, M. Fujita, R. Nakashima, Y. Ueda, Y. Ueno, T. Miyatake, T. Yoshizaki, G. S. Buzard, et al. (2005)
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D. T. Marie-Egyptienne, M. A. Cerone, J. A. Londono-Vallejo, and C. Autexier (2005)
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Human Telomerase RNA Template Sequence Is a Determinant of Telomere Repeat Extension Rate.
W. C. Drosopoulos, R. DiRenzo, and V. R. Prasad (2005)
J. Biol. Chem. 280, 32801-32810
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Function of AP-1 in Transcription of the Telomerase Reverse Transcriptase Gene (TERT) in Human and Mouse Cells.
M. Takakura, S. Kyo, M. Inoue, W. E. Wright, and J. W. Shay (2005)
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S Bravaccini, M A Sanchini, A Amadori, L Medri, L Saragoni, D Calistri, F Monti, A Volpi, and D Amadori (2005)
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L. Riou, H. Bastos, B. Lassalle, M. Coureuil, J. Testart, F. D. Boussin, I. Allemand, and P. Fouchet (2005)
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Expression of human telomerase catalytic protein in gallbladder carcinogenesis.
B Luzar, M Poljak, A Cor, U Klopcic, and V Ferlan-Marolt (2005)
J. Clin. Pathol. 58, 820-825
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Cellular and Gene Expression Responses Involved in the Rapid Growth Inhibition of Human Cancer Cells by RNA Interference-mediated Depletion of Telomerase RNA.
S. Li, J. Crothers, C. M. Haqq, and E. H. Blackburn (2005)
J. Biol. Chem. 280, 23709-23717
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R. Nuzzo (2005)
PNAS 102, 8077-8079
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Senescence and immortalization: role of telomeres and telomerase.
J. W. Shay and W. E. Wright (2005)
Carcinogenesis 26, 867-874
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X. Liu, H. Yuan, B. Fu, G. L. Disbrow, T. Apolinario, V. Tomaic, M. L. Kelley, C. C. Baker, J. Huibregtse, and R. Schlegel (2005)
J. Biol. Chem. 280, 10807-10816
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H. El-Daly, M. Kull, S. Zimmermann, M. Pantic, C. F. Waller, and U. M. Martens (2005)
Blood 105, 1742-1749
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Identification of two distinct elements mediating activation of telomerase (hTERT) gene expression in association with cell growth in human T cells.
Y. Matsumura-Arioka, K. Ohtani, T. Hara, R. Iwanaga, and M. Nakamura (2005)
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M. ARMANIOS and C.W. GREIDER (2005)
Cold Spring Harb Symp Quant Biol 70, 205-208
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Processive Utilization of the Human Telomerase Template: LACK OF A REQUIREMENT FOR TEMPLATE SWITCHING.
M. A. Rivera and E. H. Blackburn (2004)
J. Biol. Chem. 279, 53770-53781
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Heterozygous telomerase RNA mutations found in dyskeratosis congenita and aplastic anemia reduce telomerase activity via haploinsufficiency.
A. Marrone, D. Stevens, T. Vulliamy, I. Dokal, and P. J. Mason (2004)
Blood 104, 3936-3942
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p53-dependent Down-regulation of Telomerase Is Mediated by p21waf1.
I. Shats, M. Milyavsky, X. Tang, P. Stambolsky, N. Erez, R. Brosh, I. Kogan, I. Braunstein, M. Tzukerman, D. Ginsberg, et al. (2004)
J. Biol. Chem. 279, 50976-50985
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Nucleolin Interacts with Telomerase.
S. Khurts, K. Masutomi, L. Delgermaa, K. Arai, N. Oishi, H. Mizuno, N. Hayashi, W. C. Hahn, and S. Murakami (2004)
J. Biol. Chem. 279, 51508-51515
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Telomerase as a new target for the treatment of hormone-refractory prostate cancer.
A. Biroccio and C. Leonetti (2004)
Endocr. Relat. Cancer 11, 407-421
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Telomere-based DNA damage responses: a new approach to melanoma.
N. PURI, M. S. ELLER, H. R. BYERS, S. DYKSTRA, J. KUBERA, and B. A. GILCHREST (2004)
FASEB J 18, 1373-1381
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Correlation between telomerase expression and terminal restriction fragment length ratio in non-small cell lung cancer--an adjusted measurement and its clinical significance.
C. P. Hsu, J. Miaw, S. E. Shai, and C. Y. Chen (2004)
Eur. J. Cardiothorac. Surg. 26, 425-431
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Antitumor Activity of Systemically Delivered Ribozymes Targeting Murine Telomerase RNA.
M. Nosrati, S. Li, S. Bagheri, D. Ginzinger, E. H. Blackburn, R. J. Debs, and M. Kashani-Sabet (2004)
Clin. Cancer Res. 10, 4983-4990
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Rapid Inhibition of Cancer Cell Growth Induced by Lentiviral Delivery and Expression of Mutant-Template Telomerase RNA and Anti-telomerase Short-Interfering RNA.
S. Li, J. E. Rosenberg, A. A. Donjacour, I. L. Botchkina, Y. K. Hom, G. R. Cunha, and E. H. Blackburn (2004)
Cancer Res. 64, 4833-4840
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Induction of Telomerase Activity in Avian Lymphoblastoid Cell Line Transformed by Marek's Disease Virus, MDCC-MSB1.
A. D.-A. Lounis, D. Soubieux, W. Klapper, and D. Rasschaert (2004)
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Chromosome in situ hybridisation, Ki-67, and telomerase immunocytochemistry in liquid based cervical cytology.
A N Y Cheung, P M Chiu, K L Tsun, U S Khoo, B S Y Leung, and H Y S Ngan (2004)
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Template Requirements for Telomerase Translocation in Kluyveromyces lactis.
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Mol. Cell. Biol. 24, 912-923
   Abstract »    Full Text »    PDF »
Telomere maintenance in childhood primitive neuroectodermal brain tumors.
D. Didiano, T. Shalaby, D. Lang, and M. A. Grotzer (2004)
Neuro-oncol 6, 1-8
   Abstract »    PDF »
Analysis of a long-range interaction between conserved domains of human telomerase RNA.
C. T. UEDA and R. W. ROBERTS (2004)
RNA 10, 139-147
   Abstract »    Full Text »    PDF »
Telomerase RNA Accumulates in Cajal Bodies in Human Cancer Cells.
Y. Zhu, R. L. Tomlinson, A. A. Lukowiak, R. M. Terns, and M. P. Terns (2004)
Mol. Biol. Cell 15, 81-90
   Abstract »    Full Text »    PDF »
BRCA1 Inhibition of Telomerase Activity in Cultured Cells.
J. Xiong, S. Fan, Q. Meng, L. Schramm, C. Wang, B. Bouzahza, J. Zhou, B. Zafonte, I. D. Goldberg, B. R. Haddad, et al. (2003)
Mol. Cell. Biol. 23, 8668-8690
   Abstract »    Full Text »    PDF »
Successful Immortalization of Endometrial Glandular Cells with Normal Structural and Functional Characteristics.
S. Kyo, M. Nakamura, T. Kiyono, Y. Maida, T. Kanaya, M. Tanaka, N. Yatabe, and M. Inoue (2003)
Am. J. Pathol. 163, 2259-2269
   Abstract »    Full Text »
Small Interfering RNA-Mediated Reduction in Heterogeneous Nuclear Ribonucleoparticule A1/A2 Proteins Induces Apoptosis in Human Cancer Cells but not in Normal Mortal Cell Lines.
C. Patry, L. Bouchard, P. Labrecque, D. Gendron, B. Lemieux, J. Toutant, E. Lapointe, R. Wellinger, and B. Chabot (2003)
Cancer Res. 63, 7679-7688
   Abstract »    Full Text »    PDF »
Eyes Wide Open.
I. Chen (2003)
Sci. Aging Knowl. Environ. 2003, nf19
   Abstract »    Full Text »


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