Telomerase Reverse Transcriptase Regulates microRNAs
Abstract
:1. Introduction
2. Results
2.1. Screening of Short RNAs Regulated by Telomerase Reverse Transcriptase (TERT)
2.2. Validating TERT-Based miRNA Regulation
2.3. Direct versus Indirect Regulation of miRNAs by TERT
2.4. TERT May Regulate miRNAs in Cooperation with BRG1 and NS
3. Discussion
4. Experimental Section
4.1. Cell Culture
4.2. siRNA Transfection, RNA Extraction and Expression Analysis by RT-qPCR
4.3. shRNA Transduction, RNA Extraction and Expression Analysis by RT-qPCR
4.4. Library Construction and Sequencing
4.5. Bioinformatics
4.6. Purification of TERT Complexes and Isolation of RNAs
5. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
- Bartel, D.P. MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell 2004, 116, 281–297. [Google Scholar] [CrossRef] [PubMed]
- Siomi, H.; Siomi, M.C. Posttranscriptional regulation of microRNA biogenesis in animals. Mol. Cell 2010, 38, 323–332. [Google Scholar] [CrossRef] [PubMed]
- O’Donnell, K.A.; Wentzel, E.A.; Zeller, K.I.; Dang, C.V.; Mendell, J.T. c-Myc-regulated microRNAs modulate E2F1 expression. Nature 2005, 435, 839–843. [Google Scholar] [CrossRef] [PubMed]
- Loffler, D.; Brocke-Heidrich, K.; Pfeifer, G.; Stocsits, C.; Hackermuller, J.; Kretzschmar, A.K.; Burger, R.; Gramatzki, M.; Blumert, C.; Bauer, K.; et al. Interleukin-6 dependent survival of multiple myeloma cells involves the Stat3-mediated induction of microRNA-21 through a highly conserved enhancer. Blood 2007, 110, 1330–1333. [Google Scholar] [CrossRef] [PubMed]
- Brock, M.; Trenkmann, M.; Gay, R.E.; Michel, B.A.; Gay, S.; Fischler, M.; Ulrich, S.; Speich, R.; Huber, L.C. Interleukin-6 modulates the expression of the bone morphogenic protein receptor type II through a novel STAT3-microRNA cluster 17/92 pathway. Circ. Res. 2009, 104, 1184–1191. [Google Scholar] [CrossRef] [PubMed]
- Iliopoulos, D.; Jaeger, S.A.; Hirsch, H.A.; Bulyk, M.L.; Struhl, K. STAT3 activation of miR-21 and miR-181b-1 via PTEN and CYLD are part of the epigenetic switch linking inflammation to cancer. Mol. Cell 2010, 39, 493–506. [Google Scholar] [CrossRef] [PubMed]
- Ma, L.; Teruya-Feldstein, J.; Weinberg, R.A. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 2007, 449, 682–688. [Google Scholar] [CrossRef] [PubMed]
- Lee, Y.B.; Bantounas, I.; Lee, D.Y.; Phylactou, L.; Caldwell, M.A.; Uney, J.B. Twist-1 regulates the miR-199a/214 cluster during development. Nucleic Acids Res. 2009, 37, 123–128. [Google Scholar] [CrossRef] [PubMed]
- Taganov, K.D.; Boldin, M.P.; Chang, K.J.; Baltimore, D. NF-κB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc. Natl. Acad. Sci. USA 2006, 103, 12481–12486. [Google Scholar] [CrossRef] [PubMed]
- Baer, C.; Claus, R.; Plass, C. Genome-wide epigenetic regulation of miRNAs in cancer. Cancer Res. 2013, 73, 473–477. [Google Scholar] [CrossRef] [PubMed]
- Weinrich, S.L.; Pruzan, R.; Ma, L.; Ouellette, M.; Tesmer, V.M.; Holt, S.E.; Bodnar, A.G.; Lichtsteiner, S.; Kim, N.W.; Trager, J.B.; et al. Reconstitution of human telomerase with the template RNA component hTR and the catalytic protein subunit hTRT. Nat. Genet. 1997, 17, 498–502. [Google Scholar] [CrossRef] [PubMed]
- Gonzalez-Suarez, E.; Samper, E.; Ramirez, A.; Flores, J.M.; Martin-Caballero, J.; Jorcano, J.L.; Blasco, M.A. Increased epidermal tumors and increased skin wound healing in transgenic mice overexpressing the catalytic subunit of telomerase, mTERT, in basal keratinocytes. EMBO J. 2001, 20, 2619–2630. [Google Scholar] [CrossRef] [PubMed]
- Artandi, S.E.; Alson, S.; Tietze, M.K.; Sharpless, N.E.; Ye, S.; Greenberg, R.A.; Castrillon, D.H.; Horner, J.W.; Weiler, S.R.; Carrasco, R.D.; et al. Constitutive telomerase expression promotes mammary carcinomas in aging mice. Proc. Natl. Acad. Sci. USA 2002, 99, 8191–8196. [Google Scholar] [CrossRef] [PubMed]
- Masutomi, K.; Possemato, R.; Wong, J.M.; Currier, J.L.; Tothova, Z.; Manola, J.B.; Ganesan, S.; Lansdorp, P.M.; Collins, K.; Hahn, W.C. The telomerase reverse transcriptase regulates chromatin state and DNA damage responses. Proc. Natl. Acad. Sci. USA 2005, 102, 8222–8227. [Google Scholar] [CrossRef] [PubMed]
- Sarin, K.Y.; Cheung, P.; Gilison, D.; Lee, E.; Tennen, R.I.; Wang, E.; Artandi, M.K.; Oro, A.E.; Artandi, S.E. Conditional telomerase induction causes proliferation of hair follicle stem cells. Nature 2005, 436, 1048–1052. [Google Scholar] [CrossRef] [PubMed]
- Lee, J.; Sung, Y.H.; Cheong, C.; Choi, Y.S.; Jeon, H.K.; Sun, W.; Hahn, W.C.; Ishikawa, F.; Lee, H.W. TERT promotes cellular and organismal survival independently of telomerase activity. Oncogene 2008, 27, 3754–3760. [Google Scholar] [CrossRef] [PubMed]
- Low, K.C.; Tergaonkar, V. Telomerase: Central regulator of all of the hallmarks of cancer. Trends. Biochem. Sci. 2013, 38, 426–434. [Google Scholar] [CrossRef] [PubMed]
- Li, Y.; Tergaonkar, V. Noncanonical functions of telomerase: Implications in telomerase-targeted cancer therapies. Cancer Res. 2014, 74, 1639–1644. [Google Scholar] [CrossRef] [PubMed]
- Maida, Y.; Yasukawa, M.; Furuuchi, M.; Lassmann, T.; Possemato, R.; Okamoto, N.; Kasim, V.; Hayashizaki, Y.; Hahn, W.C.; Masutomi, K. An RNA-dependent RNA polymerase formed by TERT and the RMRP RNA. Nature 2009, 461, 230–235. [Google Scholar] [CrossRef] [PubMed]
- Maida, Y.; Yasukawa, M.; Okamoto, N.; Ohka, S.; Kinoshita, K.; Totoki, Y.; Ito, T.K.; Minamino, T.; Nakamura, H.; Yamaguchi, S.; et al. Involvement of telomerase reverse transcriptase in heterochromatin maintenance. Mol. Cell Biol. 2014, 34, 1576–1593. [Google Scholar] [CrossRef] [PubMed]
- Okamoto, N.; Yasukawa, M.; Nguyen, C.; Kasim, V.; Maida, Y.; Possemato, R.; Shibata, T.; Ligon, K.L.; Fukami, K.; Hahn, W.C.; et al. Maintenance of tumor initiating cells of defined genetic composition by nucleostemin. Proc. Natl. Acad. Sci. USA 2011, 108, 20388–20393. [Google Scholar] [CrossRef] [PubMed]
- Kawaji, H.; Nakamura, M.; Takahashi, Y.; Sandelin, A.; Katayama, S.; Fukuda, S.; Daub, C.O.; Kai, C.; Kawai, J.; Yasuda, J.; et al. Hidden layers of human small RNAs. BMC Genomics 2008, 9. [Google Scholar] [CrossRef] [PubMed]
- Hannon, G.J.; Maroney, P.A.; Branch, A.; Benenfield, B.J.; Robertson, H.D.; Nilsen, T.W. Accurate processing of human pre-rRNA in vitro. Mol. Cell Biol. 1989, 9, 4422–4431. [Google Scholar] [PubMed]
- Burroughs, A.M.; Ando, Y.; de Hoon, M.J.; Tomaru, Y.; Nishibu, T.; Ukekawa, R.; Funakoshi, T.; Kurokawa, T.; Suzuki, H.; Hayashizaki, Y.; et al. A comprehensive survey of 3' animal miRNA modification events and a possible role for 3' adenylation in modulating miRNA targeting effectiveness. Genome Res. 2010, 20, 1398–1410. [Google Scholar] [CrossRef] [PubMed]
- Park, J.I.; Venteicher, A.S.; Hong, J.Y.; Choi, J.; Jun, S.; Shkreli, M.; Chang, W.; Meng, Z.; Cheung, P.; Ji, H.; et al. Telomerase modulates Wnt signalling by association with target gene chromatin. Nature 2009, 460, 66–72. [Google Scholar] [CrossRef] [PubMed]
- Cai, X.; Hagedorn, C.H.; Cullen, B.R. Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA 2004, 10, 1957–1966. [Google Scholar] [CrossRef] [PubMed]
- Lee, Y.; Kim, M.; Han, J.; Yeom, K.H.; Lee, S.; Baek, S.H.; Kim, V.N. MicroRNA genes are transcribed by RNA polymerase II. EMBO J. 2004, 23, 4051–4060. [Google Scholar] [CrossRef] [PubMed]
- Borchert, G.M.; Lanier, W.; Davidson, B.L. RNA polymerase III transcribes human microRNAs. Nat. Struct. Mol. Biol. 2006, 13, 1097–1101. [Google Scholar] [CrossRef] [PubMed]
- Morlando, M.; Ballarino, M.; Gromak, N.; Pagano, F.; Bozzoni, I.; Proudfoot, N.J. Primary microRNA transcripts are processed co-transcriptionally. Nat. Struct. Mol. Biol. 2008, 15, 902–909. [Google Scholar] [CrossRef] [PubMed]
- Fujita, S.; Iba, H. Putative promoter regions of miRNA genes involved in evolutionarily conserved regulatory systems among vertebrates. Bioinformatics 2008, 24, 303–308. [Google Scholar] [CrossRef] [PubMed]
- Marson, A.; Levine, S.S.; Cole, M.F.; Frampton, G.M.; Brambrink, T.; Johnstone, S.; Guenther, M.G.; Johnston, W.K.; Wernig, M.; Newman, J.; et al. Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells. Cell 2008, 134, 521–533. [Google Scholar] [CrossRef] [PubMed]
- Ozsolak, F.; Poling, L.L.; Wang, Z.; Liu, H.; Liu, X.S.; Roeder, R.G.; Zhang, X.; Song, J.S.; Fisher, D.E. Chromatin structure analyses identify miRNA promoters. Genes Dev. 2008, 22, 3172–3183. [Google Scholar] [CrossRef] [PubMed]
- Corcoran, D.L.; Pandit, K.V.; Gordon, B.; Bhattacharjee, A.; Kaminski, N.; Benos, P.V. Features of mammalian microRNA promoters emerge from polymerase II chromatin immunoprecipitation data. PLoS One 2009, 4, e5279. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Carninci, P.; Sandelin, A.; Lenhard, B.; Katayama, S.; Shimokawa, K.; Ponjavic, J.; Semple, C.A.; Taylor, M.S.; Engstrom, P.G.; Frith, M.C.; et al. Genome-wide analysis of mammalian promoter architecture and evolution. Nat. Genet. 2006, 38, 626–635. [Google Scholar] [CrossRef] [PubMed]
- Dews, M.; Homayouni, A.; Yu, D.; Murphy, D.; Sevignani, C.; Wentzel, E.; Furth, E.E.; Lee, W.M.; Enders, G.H.; Mendell, J.T.; et al. Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster. Nat. Genet. 2006, 38, 1060–1065. [Google Scholar] [CrossRef] [PubMed]
- Lin, C.H.; Jackson, A.L.; Guo, J.; Linsley, P.S.; Eisenman, R.N. Myc-regulated microRNAs attenuate embryonic stem cell differentiation. EMBO J. 2009, 28, 3157–3170. [Google Scholar] [CrossRef] [PubMed]
- Kim, J.W.; Mori, S.; Nevins, J.R. Myc-induced microRNAs integrate Myc-mediated cell proliferation and cell fate. Cancer Res. 2010, 70, 4820–4828. [Google Scholar] [CrossRef] [PubMed]
- Mestdagh, P.; Fredlund, E.; Pattyn, F.; Schulte, J.H.; Muth, D.; Vermeulen, J.; Kumps, C.; Schlierf, S.; de Preter, K.; van Roy, N.; et al. MYCN/c-MYC-induced microRNAs repress coding gene networks associated with poor outcome in MYCN/c-MYC-activated tumors. Oncogene 2010, 29, 1394–1404. [Google Scholar] [CrossRef] [PubMed]
- Smith, K.N.; Singh, A.M.; Dalton, S. Myc represses primitive endoderm differentiation in pluripotent stem cells. Cell Stem Cell 2010, 7, 343–354. [Google Scholar] [CrossRef] [PubMed]
- Card, D.A.; Hebbar, P.B.; Li, L.; Trotter, K.W.; Komatsu, Y.; Mishina, Y.; Archer, T.K. Oct4/Sox2-regulated miR-302 targets cyclin D1 in human embryonic stem cells. Mol. Cell Biol. 2008, 28, 6426–6438. [Google Scholar] [CrossRef] [PubMed]
- Liu, H.; Deng, S.; Zhao, Z.; Zhang, H.; Xiao, J.; Song, W.; Gao, F.; Guan, Y. Oct4 regulates the miR-302 cluster in P19 mouse embryonic carcinoma cells. Mol. Biol. Rep. 2011, 38, 2155–2160. [Google Scholar] [CrossRef] [PubMed]
- Fujita, S.; Ito, T.; Mizutani, T.; Minoguchi, S.; Yamamichi, N.; Sakurai, K.; Iba, H. miR-21 Gene expression triggered by AP-1 is sustained through a double-negative feedback mechanism. J. Mol. Biol. 2008, 378, 492–504. [Google Scholar] [CrossRef] [PubMed]
- Mallappa, C.; Nasipak, B.T.; Etheridge, L.; Androphy, E.J.; Jones, S.N.; Sagerstrom, C.G.; Ohkawa, Y.; Imbalzano, A.N. Myogenic microRNA expression requires ATP-dependent chromatin remodeling enzyme function. Mol. Cell Biol. 2010, 30, 3176–3186. [Google Scholar] [CrossRef] [PubMed]
- He, T.C.; Sparks, A.B.; Rago, C.; Hermeking, H.; Zawel, L.; da Costa, L.T.; Morin, P.J.; Vogelstein, B.; Kinzler, K.W. Identification of c-MYC as a target of the APC pathway. Science 1998, 281, 1509–1512. [Google Scholar] [CrossRef] [PubMed]
- Van de Wetering, M.; Sancho, E.; Verweij, C.; de Lau, W.; Oving, I.; Hurlstone, A.; van der Horn, K.; Batlle, E.; Coudreuse, D.; Haramis, A.P.; et al. The β-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell 2002, 111, 241–250. [Google Scholar] [CrossRef] [PubMed]
- Ghosh, A.; Saginc, G.; Leow, S.C.; Khattar, E.; Shin, E.M.; Yan, T.D.; Wong, M.; Zhang, Z.; Li, G.; Sung, W.K.; et al. Telomerase directly regulates NF-κB-dependent transcription. Nat. Cell Biol. 2012, 14, 1270–1281. [Google Scholar] [CrossRef] [PubMed]
- Drevytska, T.I.; Nagibin, V.S.; Gurianova, V.L.; Kedlyan, V.R.; Moibenko, A.A.; Dosenko, V.E. Silencing of TERT decreases levels of miR-1, miR-21, miR-29a and miR-208a in cardiomyocytes. Cell Biochem. Funct. 2014, 32, 565–570. [Google Scholar] [CrossRef] [PubMed]
- Tomaru, Y.; Nakanishi, M.; Miura, H.; Kimura, Y.; Ohkawa, H.; Ohta, Y.; Hayashizaki, Y.; Suzuki, M. Identification of an inter-transcription factor regulatory network in human hepatoma cells by Matrix RNAi. Nucleic Acids Res. 2009, 37, 1049–1060. [Google Scholar] [CrossRef] [PubMed]
- Jiang, J.; Lee, E.J.; Gusev, Y.; Schmittgen, T.D. Real-time expression profiling of microRNA precursors in human cancer cell lines. Nucleic Acids Res. 2005, 33, 5394–5403. [Google Scholar] [CrossRef] [PubMed]
- Suzuki, H.I.; Yamagata, K.; Sugimoto, K.; Iwamoto, T.; Kato, S.; Miyazono, K. Modulation of microRNA processing by p53. Nature 2009, 460, 529–533. [Google Scholar] [CrossRef] [PubMed]
- Taft, R.J.; Glazov, E.A.; Cloonan, N.; Simons, C.; Stephen, S.; Faulkner, G.J.; Lassmann, T.; Forrest, A.R.; Grimmond, S.M.; Schroder, K.; et al. Tiny RNAs associated with transcription start sites in animals. Nat. Genet. 2009, 41, 572–578. [Google Scholar] [CrossRef] [PubMed]
- Lassmann, T.; Hayashizaki, Y.; Daub, C.O. TagDust—A program to eliminate artifacts from next generation sequencing data. Bioinformatics 2009, 25, 2839–2840. [Google Scholar] [CrossRef] [PubMed]
- Quinlan, A.R.; Hall, I.M. BEDTools: A flexible suite of utilities for comparing genomic features. Bioinformatics 2010, 26, 841–842. [Google Scholar] [CrossRef] [PubMed]
- Robinson, M.D.; McCarthy, D.J.; Smyth, G.K. edgeR: A Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 2010, 26, 139–140. [Google Scholar] [CrossRef] [PubMed]
- Lassmann, T. Nexalign. Available online: http://134.160.84.27/osc/english/dataresource/index.html (accessed on 2009).
© 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Lassmann, T.; Maida, Y.; Tomaru, Y.; Yasukawa, M.; Ando, Y.; Kojima, M.; Kasim, V.; Simon, C.; Daub, C.O.; Carninci, P.; et al. Telomerase Reverse Transcriptase Regulates microRNAs. Int. J. Mol. Sci. 2015, 16, 1192-1208. https://doi.org/10.3390/ijms16011192
Lassmann T, Maida Y, Tomaru Y, Yasukawa M, Ando Y, Kojima M, Kasim V, Simon C, Daub CO, Carninci P, et al. Telomerase Reverse Transcriptase Regulates microRNAs. International Journal of Molecular Sciences. 2015; 16(1):1192-1208. https://doi.org/10.3390/ijms16011192
Chicago/Turabian StyleLassmann, Timo, Yoshiko Maida, Yasuhiro Tomaru, Mami Yasukawa, Yoshinari Ando, Miki Kojima, Vivi Kasim, Christophe Simon, Carsten O. Daub, Piero Carninci, and et al. 2015. "Telomerase Reverse Transcriptase Regulates microRNAs" International Journal of Molecular Sciences 16, no. 1: 1192-1208. https://doi.org/10.3390/ijms16011192