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http://dx.doi.org/10.5483/BMBRep.2014.47.1.284

Telomerase reverse transcriptase in the regulation of gene expression  

Zhou, Junzhi (Institute of Aging Research, Hangzhou Normal University School of Medicine)
Ding, Deqiang (Institute of Aging Research, Hangzhou Normal University School of Medicine)
Wang, Miao (Institute of Aging Research, Hangzhou Normal University School of Medicine)
Cong, Yu-Sheng (Institute of Aging Research, Hangzhou Normal University School of Medicine)
Publication Information
BMB Reports / v.47, no.1, 2014 , pp. 8-14 More about this Journal
Abstract
Telomerase plays a pivotal role in the pathology of aging and cancer by maintaining genome integrity, controlling cell proliferation, and regulating tissue homeostasis. Telomerase is essentially composed of an RNA component, Telomerase RNA or TERC, which serves as a template for telomeric DNA synthesis, and a catalytic subunit, telomerase reverse transcriptase (TERT). The canonical function of TERT is the synthesis of telomeric DNA repeats, and the maintenance of telomere length. However, accumulating evidence indicates that TERT may also have some fundamental functions that are independent of its enzymatic activity. Among these telomere-independent activities of hTERT, the role of hTERT in gene transcription has been investigated in detail. Transcriptional regulation is a fundamental process in biological systems. Several studies have shown a direct involvement of hTERT in gene transcription. This mini-review will focus on the role of hTERT in gene transcription regulation, and discuss its possible mechanisms.
Keywords
Gene expression; Telomerase; TERT;
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1 Blackburn, E. H., Greider, C. W., Henderson, E., Lee, M. S., Shampay, J. and Shippen-Lentz, D. (1989) Recognition and elongation of telomeres by telomerase. Genome 31, 553-560.   DOI   ScienceOn
2 Verdun, R. E. and Karlseder, J. (2007) Replication and protection of telomeres. Nature 447, 924-931.   DOI   ScienceOn
3 Harley, C. B. (2008) Telomerase and cancer therapeutics. Nat. Rev. Cancer 8, 167-179.   DOI   ScienceOn
4 Jaskelioff, M., Muller, F. L., Paik, J. H., Thomas, E., Jiang, S., Adams, A. C., Sahin, E., Kost-Alimova, M., Protopopov, A., Cadinanos, J., Horner, J. W., Maratos-Flier, E. and Depinho, R. A. (2011) Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice. Nature 469, 102-106.   DOI   ScienceOn
5 Dokal, I. (2011) Dyskeratosis congenita. Hematology Am. Soc. Hematol. Educ. Program 2011, 480-486.   DOI   ScienceOn
6 Ghosh, A., Saginc, G., Leow, S. C., Khattar, E., Shin, E. M., Yan, T. D., Wong, M., Zhang, Z. Z., Li, G. L., Sung, W. K., Zhou, J. B., Chng, W. J., Li, S., Liu, E. and Tergaonkar, V. (2012) Telomerase directly regulates NF-kappa B-dependent transcription. Nat. Cell Biol. 14, 1270-1281.   DOI   ScienceOn
7 Ding, D., Xi, P., Zhou, J., Wang, M. and Cong, Y. S. (2013) Human telomerase reverse transcriptase regulates MMP expression independently of telomerase activity via NFkappaB-dependent transcription. FASEB J. 27, 4375-4383.   DOI   ScienceOn
8 Choi, J. K., Southworth, L. K., Sarin, K. Y., Venteicher, A. S., Ma, W. X., Chang, W., Cheung, P., Jun, S. H., Artandi, M. K., Shah, N., Kim, S. K. and Artandi, S. E. (2008) TERT promotes epithelial proliferation through transcriptional control of a Myc- and Wnt-related developmental program. Plos. Genet. 4, 0124-0138.
9 Zhou, J., Mao, B., Zhou, Q., Ding, D., Wang, M., Guo, P., Gao, Y., Shay, J. W., Yuan, Z. and Cong, Y. S. (2013) Endoplasmic reticulum stress activates telomerase. Aging Cell DOI: 10.1111/acel.12161.   DOI   ScienceOn
10 Fu, W., Killen, M., Culmsee, C., Dhar, S., Pandita, T. K. and Mattson, M. P. (2000) The catalytic subunit of telomerase is expressed in developing brain neurons and serves a cell survival-promoting function. J. Mol. Neurosci. 14, 3-15.   DOI   ScienceOn
11 Haendeler, J., Drose, S., Buchner, N., Jakob, S., Altschmied, J., Goy, C., Spyridopoulos, I., Zeiher, A. M., Brandt, U. and Dimmeler, S. (2009) Mitochondrial telomerase reverse transcriptase binds to and protects mitochondrial DNA and function from damage. Arterioscler. Thromb. Vasc. Biol. 29, 929-935.   DOI   ScienceOn
12 Indran, I. R., Hande, M. P. and Pervaiz, S. (2011) hTERT overexpression alleviates intracellular ROS production, improves mitochondrial function, and inhibits ROS-mediated apoptosis in cancer cells. Cancer Res. 71, 266-276.   DOI
13 Kovalenko, O. A., Caron, M. J., Ulema, P., Medrano, C., Thomas, A. P., Kimura, M., Bonini, M. G., Herbig, U. and Santos, J. H. (2010) A mutant telomerase defective in nuclear-cytoplasmic shuttling fails to immortalize cells and is associated with mitochondrial dysfunction. Aging Cell 9, 203-219.   DOI   ScienceOn
14 Cong, Y. and Shay, J. W. (2008) Actions of human telomerase beyond telomeres. Cell Res. 18, 725-732.   DOI   ScienceOn
15 Smith, L. L., Coller, H. A. and Roberts, J. M. (2003) Telomerase modulates expression of growth-controlling genes and enhances cell proliferation. Nat. Cell Biol. 5, 474-479.   DOI   ScienceOn
16 Lindvall, C., Hou, M., Komurasaki, T., Zheng, C., Henriksson, M., Sedivy, J. M., Bjorkholm, M., Teh, B. T., Nordenskjold, M. and Xu, D. (2003) Molecular characterization of human telomerase reverse transcriptase-immortalized human fibroblasts by gene expression profiling: activation of the epiregulin gene. Cancer Res. 63, 1743-1747.
17 Young, J. I., Sedivy, J. M. and Smith, J. R. (2003) Telomerase expression in normal human fibroblasts stabilizes DNA 5-methylcytosine transferase I. J. Biol. Chem. 278, 19904-19908.   DOI   ScienceOn
18 Park, Y. P., Choi, S. C., Kim, J. H., Song, E. Y., Kim, J. W., Yoon, D. Y., Yeom, Y. I., Lim, J. S., Paik, S. G. and Lee, H. G. (2007) Up-regulation of Mac-2 binding protein by hTERT in gastric cancer. Int. J. Cancer 120, 813-820.   DOI   ScienceOn
19 Jagadeesh, S. and Banerjee, P. P. (2006) Telomerase reverse transcriptase regulates the expression of a key cell cycle regulator, cyclin D1. Biochem. Biophys. Res. Commun. 347, 774-780.   DOI   ScienceOn
20 Perrault, S. D., Hornsby, P. J. and Betts, D. H. (2005) Global gene expression response to telomerase in bovine adrenocortical cells. Biochem. Biophys. Res. Commun. 335, 925-936.   DOI   ScienceOn
21 Masutomi, K., Possemato, R., Wong, J. M., Currier, J. L., Tothova, Z., Manola, J. B., Ganesan, S., Lansdorp, P. M., Collins, K. and Hahn, W. C. (2005) The telomerase reverse transcriptase regulates chromatin state and DNA damage responses. Proc. Natl. Acad. Sci. U. S. A. 102, 8222-8227.   DOI   ScienceOn
22 Hanahan, D. and Weinberg, R. A. (2000) The hallmarks of cancer. Cell 100, 57-70.   DOI   ScienceOn
23 Stewart, S. A., Hahn, W. C., O'Connor, B. F., Banner, E. N., Lundberg, A. S., Modha, P., Mizuno, H., Brooks, M. W., Fleming, M., Zimonjic, D. B., Popescu, N. C. and Weinberg, R. A. (2002) Telomerase contributes to tumori-genesis by a telomere length-independent mechanism. Proc. Natl. Acad. Sci. U. S. A. 99, 12606-12611.   DOI   ScienceOn
24 Perkins, N. D. (2012) The diverse and complex roles of NF-kappaB subunits in cancer. Nat. Rev. Cancer 12, 121-132.
25 Zuo, Q. P., Liu, S. K., Li, Z. J., Li, B., Zhou, Y. L., Guo, R. and Huang, L. H. (2011) NF-kappaB p65 modulates the telomerase reverse transcriptase in the HepG(2) hepatoma cell line. Eur. J.Pharmacol. 672, 113-120.   DOI   ScienceOn
26 Oeckinghaus, A., Hayden, M. S. and Ghosh, S. (2011) Crosstalk in NF-kappaB signaling pathways. Nat. Immunol. 12, 695-708.
27 Yin, L., Hubbard, A. K. and Giardina, C. (2000) NF-kappa B regulates transcription of the mouse telomerase catalytic subunit. J. Biol. Chem. 275, 36671-36675.   DOI   ScienceOn
28 Akiyama, M., Hideshima, T., Hayashi, T., Tai, Y. T., Mitsiades, C. S., Mitsiades, N., Chauhan, D., Richardson, P., Munshi, N. C. and Anderson, K. C. (2002) Cytokines modulate telomerase activity in a human multiple myeloma cell line. Cancer Res. 62, 3876-3882.
29 Ghosh, A., Saginc, G., Leow, S. C., Khattar, E., Shin, E. M., Yan, T. D., Wong, M., Zhang, Z., Li, G., Sung, W. K., Zhou, J., Chng, W. J., Li, S., Liu, E. and Tergaonkar, V. (2012) Telomerase directly regulates NF-kappaB-dependent transcription. Nat. Cell Biol. 14, 1270-1281.   DOI   ScienceOn
30 Rentoukas, E., Tsarouhas, K., Kaplanis, I., Korou, E., Nikolaou, M., Marathonitis, G., Kokkinou, S., Haliassos, A., Mamalaki, A., Kouretas, D. and Tsitsimpikou, C. (2012) Connection between telomerase activity in PBMC and markers of inflammation and endothelial dysfunction in patients with metabolic syndrome. PLoS One. 7, e35739.   DOI
31 Gizard, F., Heywood, E. B., Findeisen, H. M., Zhao, Y., Jones, K. L., Cudejko, C., Post, G. R., Staels, B. and Bruemmer, D. (2011) Telomerase activation in atherosclerosis and induction of telomerase reverse transcriptase expression by inflammatory stimuli in macrophages. Arterioscler. Thromb. Vasc. Biol. 31, 245-252.   DOI   ScienceOn
32 Clevers, H. (2006) Wnt/beta-catenin signaling in development and disease. Cell 127, 469-480.   DOI   ScienceOn
33 Liu, Z., Li, Q., Li, K., Chen, L., Li, W., Hou, M., Liu, T., Yang, J., Lindvall, C., Bjorkholm, M., Jia, J. and Xu, D. (2013) Telomerase reverse transcriptase promotes epithelial-mesenchymal transition and stem cell-like traits in cancer cells. Oncogene 32, 4203-4213.   DOI   ScienceOn
34 Anastas, J. N. and Moon, R. T. (2013) WNT signalling pathways as therapeutic targets in cancer. Nat. Rev. Cancer 13, 11-26.   DOI
35 Behrens, J., von Kries, J. P., Kuhl, M., Bruhn, L., Wedlich, D., Grosschedl, R. and Birchmeier, W. (1996) Functional interaction of beta-catenin with the transcription factor LEF-1. Nature 382, 638-642.   DOI   ScienceOn
36 Sarin, K. Y., Cheung, P., Gilison, D., Lee, E., Tennen, R. I., Wang, E., Artandi, M. K., Oro, A. E. and Artandi, S. E. (2005) Conditional telomerase induction causes proliferation of hair follicle stem cells. Nature 436, 1048-1052.   DOI   ScienceOn
37 Flores, I., Cayuela, M. L. and Blasco, M. A. (2005) Effects of telomerase and telomere length on epidermal stem cell behavior. Science 309, 1253-1256.   DOI   ScienceOn
38 Okamoto, N., Yasukawa, M., Nguyen, C., Kasim, V., Maida, Y., Possemato, R., Shibata, T., Ligon, K. L., Fukami, K., Hahn, W. C. and Masutomi, K. (2011) Maintenance of tumor initiating cells of defined genetic composition by nucleostemin. Proc. Natl. Acad. Sci. U. S. A. 108, 20388-20393.   DOI   ScienceOn
39 Zhang, Q., Wang, H. Y., Woetmann, A., Raghunath, P. N., Odum, N. and Wasik, M. A. (2006) STAT3 induces transcription of the DNA methyltransferase 1 gene (DNMT1) in malignant T lymphocytes. Blood 108, 1058-1064.   DOI   ScienceOn
40 Park, O. K., Schaefer, T. S. and Nathans, D. (1996) In vitro activation of Stat3 by epidermal growth factor receptor kinase. Proc. Natl. Acad. Sci. U. S. A. 93, 13704-13708.   DOI   ScienceOn
41 Strong, M. A., Vidal-Cardenas, S. L., Karim, B., Yu, H., Guo, N. and Greider, C. W. (2011) Phenotypes in mTERT(+)/(-) and mTERT(-)/(-) mice are due to short telomeres, not telomere-independent functions of telomerase reverse transcriptase. Mol. Cell. Biol. 31, 2369-2379.   DOI   ScienceOn
42 Listerman, I., Gazzaniga, F. S. and Blackburn, E. H. (2013) An investigation of the effects of the telomerase core protein TERT on Wnt signaling in human breast cancer cells. Mol. Cell. Biol. DOI: 10.1128/MCB.00844-13.   DOI   ScienceOn
43 Ding, D., Zhou, J., Wang, M. and Cong, Y. S. (2013) Implications of telomere-independent activities of telomerase reverse transcriptase in human cancer. FEBS. J. 280, 3205-3211.   DOI   ScienceOn
44 Hoffmeyer, K., Raggioli, A., Rudloff, S., Anton, R., Hierholzer, A., Del Valle, I., Hein, K., Vogt, R. and Kemler, R. (2012) Wnt/beta-catenin signaling regulates telomerase in stem cells and cancer cells. Science 336, 1549-1554.   DOI
45 Maida, Y., Yasukawa, M., Furuuchi, M., Lassmann, T., Possemato, R., Okamoto, N., Kasim, V., Hayashizaki, Y., Hahn, W. C. and Masutomi, K. (2009) An RNA-dependent RNA polymerase formed by TERT and the RMRP RNA. Nature 461, 230-235.   DOI   ScienceOn
46 Ridanpaa, M., van Eenennaam, H., Pelin, K., Chadwick, R., Johnson, C., Yuan, B., vanVenrooij, W., Pruijn, G., Salmela, R., Rockas, S., Makitie, O., Kaitila, I. and de la Chapelle, A. (2001) Mutations in the RNA component of RNase MRP cause a pleiotropic human disease, cartilage-hair hypoplasia. Cell 104, 195-203.   DOI   ScienceOn
47 Haendeler, J., Drose, S., Buchner, N., Jakob, S., Altschmied, J., Goy, C., Spyridopoulos, I., Zeiher, A. M., Brandt, U. and Dimmeler, S. (2009) Mitochondrial telo-merase reverse transcriptase binds to and protects mitochondrial DNA and function from damage. Arterioscler. Thromb. Vasc. Biol. 29, 929-935.   DOI   ScienceOn
48 Chang, D. D. and Clayton, D. A. (1987) A mammalian mitochondrial RNA processing activity contains nucleus-encoded RNA. Science 235, 1178-1184.   DOI
49 Rosenbluh, J., Nijhawan, D., Chen, Z., Wong, K. K., Masutomi, K. and Hahn, W. C. (2011) RMRP is a non-coding RNA essential for early murine development. PLoS One 6, e26270.   DOI   ScienceOn
50 Sharma, N. K., Reyes, A., Green, P., Caron, M. J., Bonini, M. G., Gordon, D. M., Holt, I. J. and Santos, J. H. (2012) Human telomerase acts as a hTR-independent reverse transcriptase in mitochondria. Nucleic Acids Res. 40, 712-725.   DOI
51 Indran, I. R., Hande, M. P. and Pervaiz, S. (2011) hTERT overexpression alleviates intracellular ROS production, improves mitochondrial function and inhibits ROS-mediated apoptosis in cancer cells. Cancer Res. 71, 266-276.   DOI
52 Massard, C., Zermati, Y., Pauleau, A. L., Larochette, N., Metivier, D., Sabatier, L., Kroemer, G. and Soria, J. C. (2006) hTERT: a novel endogenous inhibitor of the mitochondrial cell death pathway. Oncogene 25, 4505-4514.   DOI   ScienceOn
53 Indran, I. R., Hande, M. P. and Pervaiz, S. (2010) Tumor cell redox state and mitochondria at the center of the non-canonical activity of telomerase reverse transcriptase. Mol. Aspects. Med. 31, 21-28.   DOI   ScienceOn
54 Li, S., Crothers, J., Haqq, C. M. and Blackburn, E. H. (2005) Cellular and gene expression responses involved in the rapid growth inhibition of human cancer cells by RNA interference-mediated depleti on of telomerase RNA. J. Biol. Chem. 280, 23709-23717.   DOI   ScienceOn
55 Bagheri, S., Nosrati, M., Li, S., Fong, S., Torabian, S., Rangel, J., Moore, D. H., Federman, S., Laposa, R. R., Baehner, F. L., Sagebiel, R. W., Cleaver, J. E., Haqq, C., Debs, R. J., Blackburn, E. H. and Kashani-Sabet, M. (2006) Genes and pathways downstream of telomerase in melanoma metastasis. Proc. Natl. Acad. Sci. U. S. A. 103, 11306-11311.   DOI   ScienceOn
56 Park, J. I., Venteicher, A. S., Hong, J. Y., Choi, J., Jun, S., Shkreli, M., Chang, W., Meng, Z., Cheung, P., Ji, H., McLaughlin, M., Veenstra, T. D., Nusse, R., McCrea, P. D. and Artandi, S. E. (2009) Telomerase modulates Wnt signalling by association with target gene chromatin. Nature 460, 66-72.   DOI   ScienceOn
57 Zhou, L., Zheng, D., Wang, M. and Cong, Y. S. (2009) Telomerase reverse transcriptase activates the expression of vascular endothelial growth factor independent of telomerase activity. Biochem. Biophys. Res. Commun. 386, 739-743.   DOI   ScienceOn