Telomeric repeat-containing RNA TERRA: A noncoding RNA connecting telomere biology to genome integrity

Frontiers in Genetics

Volumn 6, Issue MAR, 2015, Pages

  Cusanelli, Emilio ^a   Chartrand, Pascal ^b  

^a UNIVERSITY OF VIENNA   (Austria)

^b UNIVERSITÉ DE MONTRÉAL   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

GENOMIC DNA; HETEROCHROMATIN PROTEIN 1; HISTONE METHYLTRANSFERASE; REPLICATION FACTOR A; RNA POLYMERASE II; TELOMERASE; TELOMERE BINDING PROTEIN; TELOMERIC REPEAT CONTAINING RNA TERRA; UNCLASSIFIED DRUG; UNTRANSLATED RNA;

ARTICLE; CELL CYCLE; DNA DAMAGE; DNA REPAIR; DNA REPLICATION; DNA TRANSCRIPTION; ENZYME ACTIVITY; GENOME; GENOMIC INSTABILITY; HETEROCHROMATIN; HUMAN; NONHUMAN; PROTEIN EXPRESSION; TELOMERE HOMEOSTASIS;

EID: 84927128325     PISSN: None     EISSN: 16648021     Source Type: Journal    
DOI: 10.3389/fgene.2015.00143     Document Type: Article

References (95)

1. Doksani, Y. & de Lange, T. The Role of Double-Strand Break Repair Pathways at Functional and Dysfunctional Telomeres. Cold Spring Harbor perspectives in biology 6, doi:10.1101/cshperspect.a016576 (2014).
2. Jain, D. & Cooper, J. P. Telomeric strategies: means to an end. Annual review of genetics 44, 243-269, doi:10.1146/annurev-genet-102108-134841 (2010).
3. Hug, N. & Lingner, J. Telomere length homeostasis. Chromosoma 115, 413-425, doi:10.1007/s00412-006-0067-3 (2006).
4. Deng, Y., Chan, S. S. & Chang, S. Telomere dysfunction and tumour suppression: the senescence connection. Nature reviews. Cancer 8, 450-458, doi:10.1038/nrc2393 (2008).
5. Greider, C. W. & Blackburn, E. H. Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 43, 405-413 (1985).
6. Allsopp, R. C. et al. Telomere Length Predicts Replicative Capacity of Human Fibroblasts. Proceedings of the National Academy of Sciences of the United States of America 89, 10114-10118, doi:DOI 10.1073/pnas.89.21.10114 (1992).
7. Bodnar, A. G. et al. Extension of life-span by introduction of telomerase into normal human cells. Science 279, 349-352 (1998).
8. Kim, N. W. et al. Specific association of human telomerase activity with immortal cells and cancer. Science 266, 2011-2015 (1994).
9. Doksani, Y., Wu, J. Y., de Lange, T. & Zhuang, X. Super-resolution fluorescence imaging of telomeres reveals TRF2-dependent T-loop formation. Cell 155, 345-356, doi:10.1016/j.cell.2013.09.048 (2013).
10. Griffith, J. D. et al. Mammalian telomeres end in a large duplex loop. Cell 97, 503-514 (1999).
11. de Lange, T. How telomeres solve the end-protection problem. Science 326, 948-952, doi:10.1126/science.1170633 (2009).
12. de Lange, T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes & development 19, 2100-2110, doi:10.1101/gad.1346005 (2005).
13. Palm, W. & de Lange, T. How shelterin protects mammalian telomeres. Annual review of genetics 42, 301-334, doi:10.1146/annurev.genet.41.110306.130350 (2008).
14. Sfeir, A. & de Lange, T. Removal of shelterin reveals the telomere end-protection problem. Science 336, 593-597, doi:10.1126/science.1218498 (2012).
15. Denchi, E. L. & de Lange, T. Protection of telomeres through independent control of ATM and ATR by TRF2 and POT1. Nature 448, 1068-1071, doi:10.1038/nature06065 (2007).
16. Karlseder, J. et al. The telomeric protein TRF2 binds the ATM kinase and can inhibit the ATMdependent DNA damage response. PLoS biology 2, E240, doi:10.1371/journal.pbio.0020240 (2004).
17. Sfeir, A. et al. Mammalian telomeres resemble fragile sites and require TRF1 for efficient replication. Cell 138, 90-103, doi:10.1016/j.cell.2009.06.021 (2009).
18. Zimmermann, M., Kibe, T., Kabir, S. & de Lange, T. TRF1 negotiates TTAGGG repeat-associated replication problems by recruiting the BLM helicase and the TPP1/POT1 repressor of ATR signaling. Genes & development 28, 2477-2491, doi:10.1101/gad.251611.114 (2014).
19. Frescas, D. & de Lange, T. TRF2-tethered TIN2 can mediate telomere protection by TPP1/POT1. Molecular and cellular biology 34, 1349-1362, doi:10.1128/MCB.01052-13 (2014).
20. Frescas, D. & de Lange, T. Binding of TPP1 protein to TIN2 protein is required for POT1a,b protein-mediated telomere protection. The Journal of biological chemistry 289, 24180-24187, doi:10.1074/jbc.M114.592592 (2014).
21. Takai, K. K., Kibe, T., Donigian, J. R., Frescas, D. & de Lange, T. Telomere protection by TPP1/POT1 requires tethering to TIN2. Molecular cell 44, 647-659, doi:10.1016/j.molcel.2011.08.043 (2011).
22. Kabir, S., Hockemeyer, D. & de Lange, T. TALEN Gene Knockouts Reveal No Requirement for the Conserved Human Shelterin Protein Rap1 in Telomere Protection and Length Regulation. Cell reports 9, 1273-1280, doi:10.1016/j.celrep.2014.10.014 (2014).
23. Gonzalo, S. et al. DNA methyltransferases control telomere length and telomere recombination in mammalian cells. Nature cell biology 8, 416-424, doi:10.1038/ncb1386 (2006).
24. Schoeftner, S. & Blasco, M. A. Chromatin regulation and non-coding RNAs at mammalian telomeres. Seminars in cell & developmental biology 21, 186-193, doi:10.1016/j.semcdb.2009.09.015 (2010).
25. Benetti, R., Garcia-Cao, M. & Blasco, M. A. Telomere length regulates the epigenetic status of mammalian telomeres and subtelomeres. Nature genetics 39, 243-250, doi:10.1038/ng1952 (2007).
26. Mason, J. M., Frydrychova, R. C. & Biessmann, H. Drosophila telomeres: an exception providing new insights. BioEssays: news and reviews in molecular, cellular and developmental biology 30, 25-37, doi:10.1002/bies.20688 (2008).
27. Rusche, L. N., Kirchmaier, A. L. & Rine, J. Ordered nucleation and spreading of silenced chromatin in Saccharomyces cerevisiae. Molecular biology of the cell 13, 2207-2222, doi:10.1091/mbc.E02-03-0175 (2002).
28. Baur, J. A., Zou, Y., Shay, J. W. & Wright, W. E. Telomere position effect in human cells. Science 292, 2075-2077, doi:10.1126/science.1062329 (2001).
29. Koering, C. E. et al. Human telomeric position effect is determined by chromosomal context and telomeric chromatin integrity. EMBO reports 3, 1055-1061, doi:10.1093/embo-reports/kvf215 (2002).
30. Schoeftner, S. & Blasco, M. A. Developmentally regulated transcription of mammalian telomeres by DNA-dependent RNA polymerase II. Nature cell biology 10, 228-236, doi:10.1038/ncb1685 (2008).
31. Azzalin, C. M., Reichenbach, P., Khoriauli, L., Giulotto, E. & Lingner, J. Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends. Science 318, 798-801, doi:10.1126/science.1147182 (2007).
32. Luke, B. et al. The Rat1p 5' to 3' exonuclease degrades telomeric repeat-containing RNA and promotes telomere elongation in Saccharomyces cerevisiae. Molecular cell 32, 465-477, doi:10.1016/j.molcel.2008.10.019 (2008).
33. Nergadze, S. G. et al. CpG-island promoters drive transcription of human telomeres. Rna 15, 2186-2194, doi:10.1261/rna.1748309 (2009).
34. Farnung, B. O., Brun, C. M., Arora, R., Lorenzi, L. E. & Azzalin, C. M. Telomerase efficiently elongates highly transcribing telomeres in human cancer cells. PloS one 7, e35714, doi:10.1371/journal.pone.0035714 (2012).
35. Yehezkel, S., Segev, Y., Viegas-Pequignot, E., Skorecki, K. & Selig, S. Hypomethylation of subtelomeric regions in ICF syndrome is associated with abnormally short telomeres and enhanced transcription from telomeric regions. Human molecular genetics 17, 2776-2789, doi:10.1093/hmg/ddn177 (2008).
36. Ng, L. J., Cropley, J. E., Pickett, H. A., Reddel, R. R. & Suter, C. M. Telomerase activity is associated with an increase in DNA methylation at the proximal subtelomere and a reduction in telomeric transcription. Nucleic acids research 37, 1152-1159, doi:10.1093/nar/gkn1030 (2009).
37. Porro, A. et al. Functional characterization of the TERRA transcriptome at damaged telomeres. Nature communications 5, 5379, doi:10.1038/ncomms6379 (2014).
38. Arnoult, N., Van Beneden, A. & Decottignies, A. Telomere length regulates TERRA levels through increased trimethylation of telomeric H3K9 and HP1alpha. Nature structural & molecular biology 19, 948-956, doi:10.1038/nsmb.2364 (2012).
39. Iglesias, N. et al. Subtelomeric repetitive elements determine TERRA regulation by Rap1/Rif and Rap1/Sir complexes in yeast. EMBO reports 12, 587-593, doi:10.1038/embor.2011.73 (2011).
40. Caslini, C., Connelly, J. A., Serna, A., Broccoli, D. & Hess, J. L. MLL associates with telomeres and regulates telomeric repeat-containing RNA transcription. Molecular and cellular biology 29, 4519-4526, doi:10.1128/MCB.00195-09 (2009).
41. Azzalin, C. M. & Lingner, J. Telomeres: the silence is broken. Cell cycle 7, 1161-1165 (2008).
42. Cusanelli, E. & Chartrand, P. Telomeric noncoding RNA: telomeric repeat-containing RNA in telomere biology. Wiley interdisciplinary reviews. RNA, doi:10.1002/wrna.1220 (2014).
43. Azzalin, C. M. & Lingner, J. Telomere functions grounding on TERRA firma. Trends in cell biology, doi:10.1016/j.tcb.2014.08.007 (2014).
44. Maicher, A., Lockhart, A. & Luke, B. Breaking new ground: digging into TERRA function. Biochimica et biophysica acta 1839, 387-394, doi:10.1016/j.bbagrm.2014.03.012 (2014).
45. de Silanes, I. L. et al. Identification of TERRA locus unveils a telomere protection role through association to nearly all chromosomes. Nature communications 5, 4723, doi:10.1038/ncomms5723 (2014).
46. Cusanelli, E., Romero, C. A. & Chartrand, P. Telomeric noncoding RNA TERRA is induced by telomere shortening to nucleate telomerase molecules at short telomeres. Molecular cell 51, 780-791, doi:10.1016/j.molcel.2013.08.029 (2013).
47. Lai, L. T., Lee, P. J. & Zhang, L. F. Immunofluorescence protects RNA signals in simultaneous RNADNA FISH. Experimental cell research 319, 46-55, doi:10.1016/j.yexcr.2012.11.009 (2013).
48. Porro, A., Feuerhahn, S., Reichenbach, P. & Lingner, J. Molecular dissection of telomeric repeatcontaining RNA biogenesis unveils the presence of distinct and multiple regulatory pathways. Molecular and cellular biology 30, 4808-4817, doi:10.1128/MCB.00460-10 (2010).
49. Lopez de Silanes, I., Stagno d'Alcontres, M. & Blasco, M. A. TERRA transcripts are bound by a complex array of RNA-binding proteins. Nature communications 1, 33, doi:10.1038/ncomms1032 (2010).
50. Deng, Z., Norseen, J., Wiedmer, A., Riethman, H. & Lieberman, P. M. TERRA RNA binding to TRF2 facilitates heterochromatin formation and ORC recruitment at telomeres. Molecular cell 35, 403-413, doi:10.1016/j.molcel.2009.06.025 (2009).
51. Scheibe, M. et al. Quantitative interaction screen of telomeric repeat-containing RNA reveals novel TERRA regulators. Genome research 23, 2149-2157, doi:10.1101/gr.151878.112 (2013).
52. Balk, B. et al. Telomeric RNA-DNA hybrids affect telomere-length dynamics and senescence. Nature structural & molecular biology 20, 1199-1205, doi:10.1038/nsmb.2662 (2013).
53. Yu, T. Y., Kao, Y. W. & Lin, J. J. Telomeric transcripts stimulate telomere recombination to suppress senescence in cells lacking telomerase. Proceedings of the National Academy of Sciences of the United States of America 111, 3377-3382, doi:10.1073/pnas.1307415111 (2014).
54. Pfeiffer, V., Crittin, J., Grolimund, L. & Lingner, J. The THO complex component Thp2 counteracts telomeric R-loops and telomere shortening. Embo J 32, 2861-2871, doi:10.1038/emboj.2013.217 (2013).
55. Arora, R. et al. RNaseH1 regulates TERRA-telomeric DNA hybrids and telomere maintenance in ALT tumour cells. Nature communications 5, 5220, doi:10.1038/ncomms6220 (2014).
56. Aguilera, A. & Garcia-Muse, T. R loops: from transcription byproducts to threats to genome stability. Molecular cell 46, 115-124, doi:10.1016/j.molcel.2012.04.009 (2012).
57. Skourti-Stathaki, K., Proudfoot, N. J. & Gromak, N. Human senataxin resolves RNA/DNA hybrids formed at transcriptional pause sites to promote Xrn2-dependent termination. Molecular cell 42, 794-805, doi:10.1016/j.molcel.2011.04.026 (2011).
58. Ginno, P. A., Lott, P. L., Christensen, H. C., Korf, I. & Chedin, F. R-loop formation is a distinctive characteristic of unmethylated human CpG island promoters. Molecular cell 45, 814-825, doi:10.1016/j.molcel.2012.01.017 (2012).
59. Yu, K., Chedin, F., Hsieh, C. L., Wilson, T. E. & Lieber, M. R. R-loops at immunoglobulin class switch regions in the chromosomes of stimulated B cells. Nature immunology 4, 442-451, doi:10.1038/ni919 (2003).
60. Bermejo, R., Lai, M. S. & Foiani, M. Preventing replication stress to maintain genome stability: resolving conflicts between replication and transcription. Molecular cell 45, 710-718, doi:10.1016/j.molcel.2012.03.001 (2012).
61. Paeschke, K. et al. Pif1 family helicases suppress genome instability at G-quadruplex motifs. Nature 497, 458-462, doi:10.1038/nature12149 (2013).
62. Boule, J. B. & Zakian, V. A. The yeast Pif1p DNA helicase preferentially unwinds RNA DNA substrates. Nucleic acids research 35, 5809-5818, doi:10.1093/nar/gkm613 (2007).
63. Rondon, A. G., Jimeno, S. & Aguilera, A. The interface between transcription and mRNP export: from THO to THSC/TREX-2. Biochimica et biophysica acta 1799, 533-538, doi:10.1016/j.bbagrm.2010.06.002 (2010).
64. Huertas, P. & Aguilera, A. Cotranscriptionally formed DNA:RNA hybrids mediate transcription elongation impairment and transcription-associated recombination. Molecular cell 12, 711-721 (2003).
65. Wellinger, R. J. & Zakian, V. A. Everything you ever wanted to know about Saccharomyces cerevisiae telomeres: beginning to end. Genetics 191, 1073-1105, doi:10.1534/genetics.111.137851 (2012).
66. Lundblad, V. & Blackburn, E. H. An alternative pathway for yeast telomere maintenance rescues est1- senescence. Cell 73, 347-360 (1993).
67. Pfeiffer, V. & Lingner, J. TERRA promotes telomere shortening through exonuclease 1-mediated resection of chromosome ends. PLoS genetics 8, e1002747, doi:10.1371/journal.pgen.1002747 (2012).
68. Bryan, T. M., Englezou, A., Gupta, J., Bacchetti, S. & Reddel, R. R. Telomere Elongation in Immortal Human-Cells without Detectable Telomerase Activity. Embo J 14, 4240-4248 (1995).
69. Conomos, D., Pickett, H. A. & Reddel, R. R. Alternative lengthening of telomeres: remodeling the telomere architecture. Frontiers in oncology 3, 27, doi:10.3389/fonc.2013.00027 (2013).
70. Dunham, M. A., Neumann, A. A., Fasching, C. L. & Reddel, R. R. Telomere maintenance by recombination in human cells. Nature genetics 26, 447-450, doi:10.1038/82586 (2000).
71. Yeager, T. R. et al. Telomerase-negative immortalized human cells contain a novel type of promyelocytic leukemia (PML) body. Cancer research 59, 4175-4179 (1999).
72. Flynn, R. L. et al. Alternative lengthening of telomeres renders cancer cells hypersensitive to ATR inhibitors. Science 347, 273-277, doi:10.1126/science.1257216 (2015).
73. Heaphy, C. M. et al. Altered telomeres in tumors with ATRX and DAXX mutations. Science 333, 425, doi:10.1126/science.1207313 (2011).
74. Schwartzentruber, J. et al. Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 482, 226-231, doi:10.1038/nature10833 (2012).
75. Lovejoy, C. A. et al. Loss of ATRX, genome instability, and an altered DNA damage response are hallmarks of the alternative lengthening of telomeres pathway. PLoS genetics 8, e1002772, doi:10.1371/journal.pgen.1002772 (2012).
76. Verdun, R. E. & Karlseder, J. The DNA damage machinery and homologous recombination pathway act consecutively to protect human telomeres. Cell 127, 709-720, doi:10.1016/j.cell.2006.09.034 (2006).
77. Zou, L. & Elledge, S. J. Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science 300, 1542-1548, doi:10.1126/science.1083430 (2003).
78. Flynn, R. L. et al. TERRA and hnRNPA1 orchestrate an RPA-to-POT1 switch on telomeric singlestranded DNA. Nature 471, 532-536, doi:10.1038/nature09772 (2011).
79. Deng, Z. et al. A role for CTCF and cohesin in subtelomere chromatin organization, TERRA transcription, and telomere end protection. Embo J 31, 4165-4178, doi:10.1038/emboj.2012.266 (2012).
80. Takai, H., Smogorzewska, A. & de Lange, T. DNA damage foci at dysfunctional telomeres. Current biology: CB 13, 1549-1556 (2003).
81. Porro, A., Feuerhahn, S. & Lingner, J. TERRA-reinforced association of LSD1 with MRE11 promotes processing of uncapped telomeres. Cell reports 6, 765-776, doi:10.1016/j.celrep.2014.01.022 (2014).
82. Poulet, A. et al. The N-terminal domains of TRF1 and TRF2 regulate their ability to condense telomeric DNA. Nucleic acids research 40, 2566-2576, doi:10.1093/nar/gkr1116 (2012).
83. Deng, Y., Guo, X., Ferguson, D. O. & Chang, S. Multiple roles for MRE11 at uncapped telomeres. Nature 460, 914-918, doi:10.1038/nature08196 (2009).
84. van Steensel, B., Smogorzewska, A. & de Lange, T. TRF2 protects human telomeres from end-toend fusions. Cell 92, 401-413 (1998).
85. Bartocci, C. et al. Isolation of chromatin from dysfunctional telomeres reveals an important role for Ring1b in NHEJ-mediated chromosome fusions. Cell reports 7, 1320-1332, doi:10.1016/j.celrep.2014.04.002 (2014).
86. Murr, R. et al. Histone acetylation by Trrap-Tip60 modulates loading of repair proteins and repair of DNA double-strand breaks. Nature cell biology 8, 91-99, doi:10.1038/ncb1343 (2006).
87. Redon, S., Reichenbach, P. & Lingner, J. The non-coding RNA TERRA is a natural ligand and direct inhibitor of human telomerase. Nucleic acids research 38, 5797-5806, doi:10.1093/nar/gkq296 (2010).
88. Gallardo, F. et al. Live cell imaging of telomerase RNA dynamics reveals cell cycle-dependent clustering of telomerase at elongating telomeres. Molecular cell 44, 819-827, doi:10.1016/j.molcel.2011.09.020 (2011).
89. d'Adda di Fagagna, F. et al. A DNA damage checkpoint response in telomere-initiated senescence. Nature 426, 194-198, doi:10.1038/nature02118 (2003).
90. Xu, G. L. et al. Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene. Nature 402, 187-191, doi:10.1038/46052 (1999).
91. Deng, Z., Campbell, A. E. & Lieberman, P. M. TERRA, CpG methylation and telomere heterochromatin: lessons from ICF syndrome cells. Cell cycle 9, 69-74 (2010).
92. Harley, C. B. Telomerase and cancer therapeutics. Nature reviews. Cancer 8, 167-179, doi:10.1038/nrc2275 (2008).
93. Hu, J. et al. Antitelomerase therapy provokes ALT and mitochondrial adaptive mechanisms in cancer. Cell 148, 651-663, doi:10.1016/j.cell.2011.12.028 (2012).
94. Chen, W., Xiao, B. K., Liu, J. P., Chen, S. M. & Tao, Z. Z. Alternative lengthening of telomeres in hTERT-inhibited laryngeal cancer cells. Cancer science 101, 1769-1776, doi:10.1111/j.1349-7006.2010.01611.x (2010).
95. Deng, Z. et al. Formation of telomeric repeat-containing RNA (TERRA) foci in highly proliferating mouse cerebellar neuronal progenitors and medulloblastoma. Journal of cell science 125, 4383-4394, doi:10.1242/jcs.108118 (2012).