Skip to main content
SpringerLink
Log in

TERRA: Long Noncoding RNA at Eukaryotic Telomeres

  • Chapter
  • First Online:
Long Non-Coding RNAs

Part of the book series: Progress in Molecular and Subcellular Biology ((PMSB,volume 51))

Abstract

Telomeres protect the ends of linear eukaryotic chromosomes from being recognized as DNA double-stranded breaks, thereby maintaining the stability of our genome. The highly heterochromatic nature of telomeres had, for a long time, reinforced the idea that telomeres were transcriptionally silent. Since a few years, however, we know that DNA-dependent RNA polymerase II transcribes telomeric DNA into TElomeric Repeat-containing RNA (TERRA) molecules in a large variety of eukaryotes. In this chapter, we summarize the current knowledge of telomere structure and function and extensively review data accumulated on TERRA biogenesis and regulation. We also discuss putative functions of TERRA in preserving telomere stability and propose future directions for research encompassing this novel and exciting aspect of telomere biology.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Aravin AA, Lagos-Quintana M, Yalcin A, Zavolan M, Marks D, Snyder B, Gaasterland T, Meyer J, Tuschl T (2003) The small RNA profile during Drosophila melanogaster development. Dev Cell 5:337–350

    Article  PubMed  CAS  Google Scholar 

  • Artandi SE, DePinho RA (2010) Telomeres and telomerase in cancer. Carcinogenesis 31:9–18

    Article  PubMed  CAS  Google Scholar 

  • Azzalin CM, Lingner J (2006) The human RNA surveillance factor UPF1 is required for S phase progression and genome stability. Curr Biol 16:433–439

    Article  PubMed  CAS  Google Scholar 

  • Azzalin CM, Lingner J (2008) Telomeres: the silence is broken. Cell Cycle 7:1161–1165

    Article  PubMed  CAS  Google Scholar 

  • Azzalin CM, Reichenbach P, Khoriauli L, Giulotto E, Lingner J (2007) Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends. Science 318:798–801

    Article  PubMed  CAS  Google Scholar 

  • Benetti R, Garcia-Cao M, Blasco MA (2007a) Telomere length regulates the epigenetic status of mammalian telomeres and subtelomeres. Nat Genet 39:243–250

    Article  PubMed  CAS  Google Scholar 

  • Benetti R, Gonzalo S, Jaco I, Schotta G, Klatt P, Jenuwein T, Blasco MA (2007b) Suv4-20h deficiency results in telomere elongation and derepression of telomere recombination. J Cell Biol 178:925–936

    Article  PubMed  CAS  Google Scholar 

  • Benetti R, Schoeftner S, Munoz P, Blasco MA (2008) Role of TRF2 in the assembly of telomeric chromatin. Cell Cycle 7:3461–3468

    Article  PubMed  CAS  Google Scholar 

  • Bianchi A, Shore D (2008) How telomerase reaches its end: mechanism of telomerase regulation by the telomeric complex. Mol Cell 31:153–165

    Article  PubMed  CAS  Google Scholar 

  • Bisoffi M, Chakerian AE, Fore ML, Bryant JE, Hernandez JP, Moyzis RK, Griffith JK (1998) Inhibition of human telomerase by a retrovirus expressing telomeric antisense RNA. Eur J Cancer 34:1242–1249

    Article  PubMed  CAS  Google Scholar 

  • Blasco MA (2007) The epigenetic regulation of mammalian telomeres. Nat Rev Genet 8:299–309

    Article  PubMed  CAS  Google Scholar 

  • Bourns BD, Alexander MK, Smith AM, Zakian VA (1998) Sir proteins, Rif proteins, and Cdc13p bind Saccharomyces telomeres in vivo. Mol Cell Biol 18:5600–5608

    PubMed  CAS  Google Scholar 

  • Brennecke J, Aravin AA, Stark A, Dus M, Kellis M, Sachidanandam R, Hannon GJ (2007) Discrete small RNA-generating loci as master regulators of transposon activity in Drosophila. Cell 128:1089–1103

    Article  PubMed  CAS  Google Scholar 

  • Brumbaugh KM, Otterness DM, Geisen C, Oliveira V, Brognard J, Li X, Lejeune F, Tibbetts RS, Maquat LE, Abraham RT (2004) The mRNA surveillance protein hSMG-1 functions in genotoxic stress response pathways in mammalian cells. Mol Cell 14:585–598

    Article  PubMed  CAS  Google Scholar 

  • Bryan TM, Marusic L, Bacchetti S, Namba M, Reddel RR (1997) The telomere lengthening mechanism in telomerase-negative immortal human cells does not involve the telomerase RNA subunit. Hum Mol Genet 6:921–926

    Article  PubMed  CAS  Google Scholar 

  • Campisi J, Yaswen P (2009) Aging and cancer cell biology, 2009. Aging Cell 8:221–225

    Article  PubMed  CAS  Google Scholar 

  • Cao F, Li X, Hiew S, Brady H, Liu Y, Dou Y (2009) Dicer independent small RNAs associate with telomeric heterochromatin. RNA 15:1274–1281

    Article  PubMed  CAS  Google Scholar 

  • Caslini C, Connelly JA, Serna A, Broccoli D, Hess JL (2009) MLL associates with telomeres and regulates telomeric repeat-containing RNA transcription. Mol Cell Biol 29:4519–4526

    Article  PubMed  CAS  Google Scholar 

  • Celli GB, de Lange T (2005) DNA processing is not required for ATM-mediated telomere damage response after TRF2 deletion. Nat Cell Biol 7:712–718

    Article  PubMed  CAS  Google Scholar 

  • Cenci G, Rawson RB, Belloni G, Castrillon DH, Tudor M, Petrucci R, Goldberg ML, Wasserman SA, Gatti M (1997) UbcD1, a Drosophila ubiquitin-conjugating enzyme required for proper telomere behavior. Genes Dev 11:863–875

    Article  PubMed  CAS  Google Scholar 

  • Cesare AJ, Reddel RR (2010) Alternative lengthening of telomeres: models, mechanisms and implications. Nat Rev Genet 11(5):319–330

    Article  PubMed  CAS  Google Scholar 

  • Chandra A, Hughes TR, Nugent CI, Lundblad V (2001) Cdc13 both positively and negatively regulates telomere replication. Genes Dev 15:404–414

    Article  PubMed  CAS  Google Scholar 

  • Colgin LM, Baran K, Baumann P, Cech TR, Reddel RR (2003) Human POT1 facilitates telomere elongation by telomerase. Curr Biol 13:942–946

    Article  PubMed  CAS  Google Scholar 

  • Cooper JP, Nimmo ER, Allshire RC, Cech TR (1997) Regulation of telomere length and function by a Myb-domain protein in fission yeast. Nature 385:744–747

    Article  PubMed  CAS  Google Scholar 

  • Déjardin J, Kingston RE (2009) Purification of proteins associated with specific genomic Loci. Cell 136:175–186

    Article  PubMed  CAS  Google Scholar 

  • Denchi EL, de Lange T (2007) Protection of telomeres through independent control of ATM and ATR by TRF2 and POT1. Nature 448:1068–1071

    Article  PubMed  CAS  Google Scholar 

  • Deng Z, Norseen J, Wiedmer A, Riethman H, Lieberman PM (2009) TERRA RNA binding to TRF2 facilitates heterochromatin formation and ORC recruitment at telomeres. Mol Cell 35:403–413

    Article  PubMed  CAS  Google Scholar 

  • Elsaesser SJ, Goldberg AD, Allis CD (2010) New functions for an old variant: no substitute for histone H3.3. Curr Opin Genet Dev 20(2):110–117

    Article  PubMed  CAS  Google Scholar 

  • Esteller M (2007) Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet 8:286–298

    Article  PubMed  CAS  Google Scholar 

  • Fajkus J, Kovarik A, Kralovics R, Bezdek M (1995) Organization of telomeric and subtelomeric chromatin in the higher plant Nicotiana tabacum. Mol Gen Genet 247:633–638

    Article  PubMed  CAS  Google Scholar 

  • Fanti L, Giovinazzo G, Berloco M, Pimpinelli S (1998) The heterochromatin protein 1 prevents telomere fusions in Drosophila. Mol Cell 2:527–538

    Article  PubMed  CAS  Google Scholar 

  • Ferreira MG, Cooper JP (2001) The fission yeast Taz1 protein protects chromosomes from Ku-dependent end-to-end fusions. Mol Cell 7:55–63

    Article  PubMed  CAS  Google Scholar 

  • Fisher TS, Zakian VA (2005) Ku: a multifunctional protein involved in telomere maintenance. DNA Repair (Amst) 4:1215–1226

    Article  CAS  Google Scholar 

  • Fitzgerald MS, McKnight TD, Shippen DE (1996) Characterization and developmental patterns of telomerase expression in plants. Proc Natl Acad Sci USA 93:14422–14427

    Article  PubMed  CAS  Google Scholar 

  • Fraga MF, Ballestar E, Villar-Garea A, Boix-Chornet M, Espada J, Schotta G, Bonaldi T, Haydon C, Ropero S, Petrie K, Iyer NG, Pérez-Rosado A, Calvo E, Lopez JA, Cano A, Calasanz MJ, Colomer D, Piris MA, Ahn N, Imhof A, Caldas C, Jenuwein T, Esteller M (2005) Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat Genet 37:391–400

    Article  PubMed  CAS  Google Scholar 

  • Gallego ME, Jalut N, White CI (2003) Telomerase dependence of telomere lengthening in Ku80 mutant Arabidopsis. Plant Cell 15:782–789

    Article  PubMed  CAS  Google Scholar 

  • Gao H, Cervantes RB, Mandell EK, Otero JH, Lundblad V (2007) RPA-like proteins mediate yeast telomere function. Nat Struct Mol Biol 14:208–214

    Article  PubMed  CAS  Google Scholar 

  • Gao G, Walser JC, Beaucher ML, Morciano P, Wesolowska N, Chen J, Rong YS (2010) HipHop interacts with HOAP and HP1 to protect Drosophila telomeres in a sequence-independent manner. EMBO J 29(4):819–829

    Article  PubMed  CAS  Google Scholar 

  • Garcia-Cao M, O’Sullivan R, Peters AH, Jenuwein T, Blasco MA (2004) Epigenetic regulation of telomere length in mammalian cells by the Suv39h1 and Suv39h2 histone methyltransferases. Nat Genet 36:94–99

    Article  PubMed  CAS  Google Scholar 

  • Garvik B, Carson M, Hartwell L (1995) Single-stranded DNA arising at telomeres in cdc13 mutants may constitute a specific signal for the RAD9 checkpoint. Mol Cell Biol 15:6128–6138

    PubMed  CAS  Google Scholar 

  • Goldberg AD, Banaszynski LA, Noh KM, Lewis PW, Elsaesser SJ, Stadler S, Dewell S, Law M, Guo X, Li X, Wen D, Chapgier A, DeKelver RC, Miller JC, Lee YL, Boydston EA, Holmes MC, Gregory PD, Greally JM, Rafii S, Yang C, Scambler PJ, Garrick D, Gibbons RJ, Higgs DR, Cristea IM, Urnov FD, Zheng D, Allis CD (2010) Distinct factors control histone variant H3.3 localization at specific genomic regions. Cell 140:678–691

    Article  PubMed  CAS  Google Scholar 

  • Gonzalez-Suarez I, Redwood AB, Perkins SM, Vermolen B, Lichtensztejin D, Grotsky DA, Morgado-Palacin L, Gapud EJ, Sleckman BP, Sullivan T, Sage J, Stewart CL, Mai S, Gonzalo S (2009) Novel roles for A-type lamins in telomere biology and the DNA damage response pathway. EMBO J 28:2414–2427

    Article  PubMed  CAS  Google Scholar 

  • Gonzalo S, Blasco MA (2005) Role of Rb family in the epigenetic definition of chromatin. Cell Cycle 4:752–755

    Article  PubMed  CAS  Google Scholar 

  • Gonzalo S, Garcia-Cao M, Fraga MF, Schotta G, Peters AH, Cotter SE, Eguia R, Dean DC, Esteller M, Jenuwein T, Blasco MA (2005) Role of the RB1 family in stabilizing histone methylation at constitutive heterochromatin. Nat Cell Biol 7:420–428

    Article  PubMed  CAS  Google Scholar 

  • Gonzalo S, Jaco I, Fraga MF, Chen T, Li E, Esteller M, Blasco MA (2006) DNA methyltransferases control telomere length and telomere recombination in mammalian cells. Nat Cell Biol 8:416–424

    Article  PubMed  CAS  Google Scholar 

  • Grandin N, Damon C, Charbonneau M (2000) Cdc13 cooperates with the yeast Ku proteins and Stn1 to regulate telomerase recruitment. Mol Cell Biol 20:8397–8408

    Article  PubMed  CAS  Google Scholar 

  • Greider CW, Blackburn EH (1985) Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 43:405–413

    Article  PubMed  CAS  Google Scholar 

  • Harley CB, Futcher AB, Greider CW (1990) Telomeres shorten during ageing of human fibroblasts. Nature 345:458–460

    Article  PubMed  CAS  Google Scholar 

  • Ho CY, Murnane JP, Yeung AK, Ng HK, Lo AW (2008) Telomeres acquire distinct heterochromatin characteristics during siRNA-induced RNA interference in mouse cells. Curr Biol 18:183–187

    Article  PubMed  CAS  Google Scholar 

  • Hughes TR, Evans SK, Weilbaecher RG, Lundblad V (2000) The Est3 protein is a subunit of yeast telomerase. Curr Biol 10:809–812

    Article  PubMed  CAS  Google Scholar 

  • Ishikawa F, Matunis MJ, Dreyfuss G, Cech TR (1993) Nuclear proteins that bind the pre-mRNA 3′ splice site sequence r(UUAG/G) and the human telomeric DNA sequence d(TTAGGG)n. Mol Cell Biol 13:4301–4310

    PubMed  CAS  Google Scholar 

  • Jinek M, Doudna JA (2009) A three-dimensional view of the molecular machinery of RNA interference. Nature 457:405–412

    Article  PubMed  CAS  Google Scholar 

  • Kahn T, Savitsky M, Georgiev P (2000) Attachment of HeT-A sequences to chromosomal termini in Drosophila melanogaster may occur by different mechanisms. Mol Cell Biol 20:7634–7642

    Article  PubMed  CAS  Google Scholar 

  • Karlseder J, Hoke K, Mirzoeva OK, Bakkenist C, Kastan MB, Petrini JH, de Lange T (2004) The telomeric protein TRF2 binds the ATM kinase and can inhibit the ATM-dependent DNA damage response. PLoS Biol 2:E240

    Article  PubMed  CAS  Google Scholar 

  • Kendellen MF, Barrientos KS, Counter CM (2009) POT1 association with TRF2 regulates telomere length. Mol Cell Biol 29:5611–5619

    Article  PubMed  CAS  Google Scholar 

  • Kibe T, Ono Y, Sato K, Ueno M (2007) Fission yeast Taz1 and RPA are synergistically required to prevent rapid telomere loss. Mol Biol Cell 18:2378–2387

    Article  PubMed  CAS  Google Scholar 

  • Killan A, Heller K, Kleinhofs A (1998) Development patterns of telomerase activity in barley and maize. Plant Mol Biol 37:621–628

    Article  PubMed  CAS  Google Scholar 

  • Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, Coviello GM, Wright WE, Weinrich SL, Shay JW (1994) Specific association of human telomerase activity with immortal cells and cancer. Science 266:2011–2015

    Article  PubMed  CAS  Google Scholar 

  • Kumaran RI, Spector DL (2008) A genetic locus targeted to the nuclear periphery in living cells maintains its transcriptional competence. J Cell Biol 180:51–65

    Article  PubMed  CAS  Google Scholar 

  • Kumaran RI, Thakar R, Spector DL (2008) Chromatin dynamics and gene positioning. Cell 132:929–934

    Article  PubMed  CAS  Google Scholar 

  • Kwon C, Chung IK (2004) Interaction of an Arabidopsis RNA-binding protein with plant single-stranded telomeric DNA modulates telomerase activity. J Biol Chem 279:12812–12818

    Article  PubMed  CAS  Google Scholar 

  • Kyrion G, Boakye KA, Lustig AJ (1992) C-terminal truncation of RAP1 results in the deregulation of telomere size, stability, and function in Saccharomyces cerevisiae. Mol Cell Biol 12:5159–5173

    PubMed  CAS  Google Scholar 

  • LaBranche H, Dupuis S, Ben-David Y, Bani MR, Wellinger RJ, Chabot B (1998) Telomere elongation by hnRNP A1 and a derivative that interacts with telomeric repeats and telomerase. Nat Genet 19:199–202

    Article  PubMed  CAS  Google Scholar 

  • Lachner M, O’Carroll D, Rea S, Mechtler K, Jenuwein T (2001) Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410:116–120

    Article  PubMed  CAS  Google Scholar 

  • Larrivee M, LeBel C, Wellinger RJ (2004) The generation of proper constitutive G-tails on yeast telomeres is dependent on the MRX complex. Genes Dev 18:1391–1396

    Article  PubMed  CAS  Google Scholar 

  • Latrick CM, Cech TR (2010) POT1-TPP1 enhances telomerase processivity by slowing primer dissociation and aiding translocation. EMBO J 29(5):924–933

    Article  PubMed  CAS  Google Scholar 

  • Lei M, Podell ER, Cech TR (2004) Structure of human POT1 bound to telomeric single-stranded DNA provides a model for chromosome end-protection. Nat Struct Mol Biol 11:1223–1229

    Article  PubMed  CAS  Google Scholar 

  • Leonardi J, Box JA, Bunch JT, Baumann P (2008) TER1, the RNA subunit of fission yeast telomerase. Nat Struct Mol Biol 15:26–33

    Article  PubMed  CAS  Google Scholar 

  • Li B, Oestreich S, de Lange T (2000) Identification of human Rap1: implications for telomere evolution. Cell 101:471–483

    Article  PubMed  CAS  Google Scholar 

  • Lin JJ, Zakian VA (1996) The Saccharomyces CDC13 protein is a single-strand TG1-3 telomeric DNA-binding protein in vitro that affects telomere behavior in vivo. Proc Natl Acad Sci USA 93:13760–13765

    Article  PubMed  CAS  Google Scholar 

  • Lingner J, Hughes TR, Shevchenko A, Mann M, Lundblad V, Cech TR (1997) Reverse transcriptase motifs in the catalytic subunit of telomerase. Science 276:561–567

    Article  PubMed  CAS  Google Scholar 

  • Liu D, Safari A, O’Connor MS, Chan DW, Laegeler A, Qin J, Songyang Z (2004) PTOP interacts with POT1 and regulates its localization to telomeres. Nat Cell Biol 6:673–680

    Article  PubMed  CAS  Google Scholar 

  • Loayza D, De Lange T (2003) POT1 as a terminal transducer of TRF1 telomere length control. Nature 423:1013–1018

    Article  PubMed  CAS  Google Scholar 

  • Longworth MS, Dyson NJ (2010) pRb, a local chromatin organizer with global possibilities. Chromosoma 119:1–11

    Article  PubMed  CAS  Google Scholar 

  • Luke B, Panza A, Redon S, Iglesias N, Li Z, Lingner J (2008) The Rat1p 5′ to 3′ exonuclease degrades telomeric repeat-containing RNA and promotes telomere elongation in Saccharomyces cerevisiae. Mol Cell 32:465–477

    Article  PubMed  CAS  Google Scholar 

  • Lundblad V, Blackburn EH (1990) RNA-dependent polymerase motifs in EST1: tentative identification of a protein component of an essential yeast telomerase. Cell 60:529–530

    Article  PubMed  CAS  Google Scholar 

  • Lundblad V, Szostak JW (1989) A mutant with a defect in telomere elongation leads to senescence in yeast. Cell 57:633–643

    Article  PubMed  CAS  Google Scholar 

  • Marcand S, Wotton D, Gilson E, Shore D (1997) Rap1p and telomere length regulation in yeast. Ciba Found Symp 211:76–93, discussion 93–103

    PubMed  CAS  Google Scholar 

  • Mason JM, Frydrychova RC, Biessmann H (2008) Drosophila telomeres: an exception providing new insights. Bioessays 30:25–37

    Article  PubMed  CAS  Google Scholar 

  • McClintock B (1941) The stability of broken ends of chromosomes in Zea mays. Genetics 26:234–282

    PubMed  CAS  Google Scholar 

  • McKay SJ, Cooke H (1992) hnRNP A2/B1 binds specifically to single stranded vertebrate telomeric repeat TTAGGGn. Nucleic Acids Res 20:6461–6464

    Article  PubMed  CAS  Google Scholar 

  • Mikhailovsky S, Belenkaya T, Georgiev P (1999) Broken chromosomal ends can be elongated by conversion in Drosophila melanogaster. Chromosoma 108:114–120

    Article  PubMed  CAS  Google Scholar 

  • Miller KM, Ferreira MG, Cooper JP (2005) Taz1, Rap1 and Rif1 act both interdependently and independently to maintain telomeres. EMBO J 24:3128–3135

    Article  PubMed  CAS  Google Scholar 

  • Miller KM, Rog O, Cooper JP (2006) Semi-conservative DNA replication through telomeres requires Taz1. Nature 440:824–828

    Article  PubMed  CAS  Google Scholar 

  • Milyavsky M, Mimran A, Senderovich S, Zurer I, Erez N, Shats I, Goldfinger N, Cohen I, Rotter V (2001) Activation of p53 protein by telomeric (TTAGGG)n repeats. Nucleic Acids Res 29:5207–5215

    Article  PubMed  CAS  Google Scholar 

  • Mitchell JR, Cheng J, Collins K (1999a) A box H/ACA small nucleolar RNA-like domain at the human telomerase RNA 3′ end. Mol Cell Biol 19:567–576

    PubMed  CAS  Google Scholar 

  • Mitchell JR, Wood E, Collins K (1999b) A telomerase component is defective in the human disease dyskeratosis congenita. Nature 402:551–555

    Article  PubMed  CAS  Google Scholar 

  • Miyoshi T, Kanoh J, Saito M, Ishikawa F (2008) Fission yeast Pot1-Tpp 1 protects telomeres and regulates telomere length. Science 320:1341–1344

    Article  PubMed  CAS  Google Scholar 

  • Muller HJ (1938) The remaking of chromosomes. Collecting Net 13:181–189

    Google Scholar 

  • Nakamura TM, Morin GB, Chapman KB, Weinrich SL, Andrews WH, Lingner J, Harley CB, Cech TR (1997) Telomerase catalytic subunit homologs from fission yeast and human. Science 277:955–959

    Article  PubMed  CAS  Google Scholar 

  • Nergadze SG, Farnung BO, Wischnewski H, Khoriauli L, Vitelli V, Chawla R, Giulotto E, Azzalin CM (2009) CpG-island promoters drive transcription of human telomeres. RNA 15:2186–2194

    Article  PubMed  CAS  Google Scholar 

  • Ng LJ, Cropley JE, Pickett HA, Reddel RR, Suter CM (2009) Telomerase activity is associated with an increase in DNA methylation at the proximal subtelomere and a reduction in telomeric transcription. Nucleic Acids Res 37:1152–1159

    Article  PubMed  CAS  Google Scholar 

  • Nicholson P, Yepiskoposyan H, Metze S, Zamudio Orozco R, Kleinschmidt N, Muhlemann O (2010) Nonsense-mediated mRNA decay in human cells: mechanistic insights, functions beyond quality control and the double-life of NMD factors. Cell Mol Life Sci 67:677–700

    Article  PubMed  CAS  Google Scholar 

  • Nugent CI, Hughes TR, Lue NF, Lundblad V (1996) Cdc13p: a single-strand telomeric DNA-binding protein with a dual role in yeast telomere maintenance. Science 274:249–252

    Article  PubMed  CAS  Google Scholar 

  • O’Connor MS, Safari A, Xin H, Liu D, Songyang Z (2006) A critical role for TPP1 and TIN2 interaction in high-order telomeric complex assembly. Proc Natl Acad Sci USA 103:11874–11879

    Article  PubMed  CAS  Google Scholar 

  • Ogawa Y, Sun BK, Lee JT (2008) Intersection of the RNA interference and X-inactivation pathways. Science 320:1336–1341

    Article  PubMed  CAS  Google Scholar 

  • Oliveira V, Romanow WJ, Geisen C, Otterness DM, Mercurio F, Wang HG, Dalton WS, Abraham RT (2008) A protective role for the human SMG-1 kinase against tumor necrosis factor-alpha-induced apoptosis. J Biol Chem 283:13174–13184

    Article  PubMed  CAS  Google Scholar 

  • Olovnikov AM (1973) A theory of marginotomy. The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon. J Theor Biol 41:181–190

    Article  PubMed  CAS  Google Scholar 

  • Palm W, de Lange T (2008) How shelterin protects mammalian telomeres. Annu Rev Genet 42:301–334

    Article  PubMed  CAS  Google Scholar 

  • Perrini B, Piacentini L, Fanti L, Altieri F, Chichiarelli S, Berloco M, Turano C, Ferraro A, Pimpinelli S (2004) HP1 controls telomere capping, telomere elongation, and telomere silencing by two different mechanisms in Drosophila. Mol Cell 15:467–476

    Article  PubMed  CAS  Google Scholar 

  • Peterson SE, Stellwagen AE, Diede SJ, Singer MS, Haimberger ZW, Johnson CO, Tzoneva M, Gottschling DE (2001) The function of a stem-loop in telomerase RNA is linked to the DNA repair protein Ku. Nat Genet 27:64–67

    PubMed  CAS  Google Scholar 

  • Petreaca RC, Chiu HC, Eckelhoefer HA, Chuang C, Xu L, Nugent CI (2006) Chromosome end protection plasticity revealed by Stn1p and Ten1p bypass of Cdc13p. Nat Cell Biol 8:748–755

    Article  PubMed  CAS  Google Scholar 

  • Qi H, Zakian VA (2000) The Saccharomyces telomere-binding protein Cdc13p interacts with both the catalytic subunit of DNA polymerase alpha and the telomerase-associated est1 protein. Genes Dev 14:1777–1788

    PubMed  CAS  Google Scholar 

  • Raffa GD, Cenci G, Siriaco G, Goldberg ML, Gatti M (2005) The putative Drosophila transcription factor woc is required to prevent telomeric fusions. Mol Cell 20:821–831

    Article  PubMed  CAS  Google Scholar 

  • Redon S, Reichenbach P, Lingner J (2007) Protein RNA and protein protein interactions mediate association of human EST1A/SMG6 with telomerase. Nucleic Acids Res 35:7011–7022

    Article  PubMed  CAS  Google Scholar 

  • Redon S, Reichenbach P, Lingner J (2010) The non-coding RNA TERRA is a natural ligand and direct inhibitor of human telomerase. Nucleic Acids Res 38(17):5797–5806

    Article  PubMed  CAS  Google Scholar 

  • Reichenbach P, Höss M, Azzalin CM, Nabholz M, Bucher P, Lingner J (2003) A human homolog of yeast Est1 associates with telomerase and uncaps chromosome ends when overexpressed. Curr Biol 13:568–574

    Article  PubMed  CAS  Google Scholar 

  • Richards EJ, Ausubel FM (1988) Isolation of a higher eukaryotic telomere from Arabidopsis thaliana. Cell 53:127–136

    Article  PubMed  CAS  Google Scholar 

  • Riethman H (2008) Human telomere structure and biology. Annu Rev Genomics Hum Genet 9:1–19

    Article  PubMed  CAS  Google Scholar 

  • Riha K, Shippen DE (2003) Telomere structure, function and maintenance in Arabidopsis. Chromosome Res 11:263–275

    Article  PubMed  CAS  Google Scholar 

  • Riha K, McKnight TD, Fajkus J, Vyskot B, Shippen DE (2000) Analysis of the G-overhang structures on plant telomeres: evidence for two distinct telomere architectures. Plant J 23:633–641

    Article  PubMed  CAS  Google Scholar 

  • Riha K, McKnight TD, Griffing LR, Shippen DE (2001) Living with genome instability: plant responses to telomere dysfunction. Science 291:1797–1800

    Article  PubMed  CAS  Google Scholar 

  • Rong YS (2008a) Loss of the histone variant H2A.Z restores capping to checkpoint-defective telomeres in Drosophila. Genetics 180:1869–1875

    Article  PubMed  CAS  Google Scholar 

  • Rong YS (2008b) Telomere capping in Drosophila: dealing with chromosome ends that most resemble DNA breaks. Chromosoma 117:235–242

    Article  PubMed  CAS  Google Scholar 

  • Saito K, Nishida KM, Mori T, Kawamura Y, Miyoshi K, Nagami T, Siomi H, Siomi MC (2006) Specific association of Piwi with rasiRNAs derived from retrotransposon and heterochromatic regions in the Drosophila genome. Genes Dev 20:2214–2222

    Article  PubMed  CAS  Google Scholar 

  • Sandell LL, Gottschling DE, Zakian VA (1994) Transcription of a yeast telomere alleviates telomere position effect without affecting chromosome stability. Proc Natl Acad Sci USA 91:12061–12065

    Article  PubMed  CAS  Google Scholar 

  • Sarthy J, Bae NS, Scrafford J, Baumann P (2009) Human RAP1 inhibits non-homologous end joining at telomeres. EMBO J 28:3390–3399

    Article  PubMed  CAS  Google Scholar 

  • Schoeftner S, Blasco MA (2008) Developmentally regulated transcription of mammalian telomeres by DNA-dependent RNA polymerase II. Nat Cell Biol 10:228–236

    Article  PubMed  CAS  Google Scholar 

  • Schotta G, Lachner M, Sarma K, Ebert A, Sengupta R, Reuter G, Reinberg D, Jenuwein T (2004) A silencing pathway to induce H3-K9 and H4-K20 trimethylation at constitutive heterochromatin. Genes Dev 18:1251–1262

    Article  PubMed  CAS  Google Scholar 

  • Seto AG, Zaug AJ, Sobel SG, Wolin SL, Cech TR (1999) Saccharomyces cerevisiae telomerase is an Sm small nuclear ribonucleoprotein particle. Nature 401:177–180

    Article  PubMed  CAS  Google Scholar 

  • Seto AG, Livengood AJ, Tzfati Y, Blackburn EH, Cech TR (2002) A bulged stem tethers Est1p to telomerase RNA in budding yeast. Genes Dev 16:2800–2812

    Article  PubMed  CAS  Google Scholar 

  • Sfeir A, Kosiyatrakul ST, Hockemeyer D, MacRae SL, Karlseder J, Schildkraut CL, de Lange T (2009) Mammalian telomeres resemble fragile sites and require TRF1 for efficient replication. Cell 138:90–103

    Article  PubMed  CAS  Google Scholar 

  • Sfeir A, Kabir S, van Overbeek M, Celli GB, de Lange T (2010) Loss of Rap1 induces telomere recombination in the absence of NHEJ or a DNA damage signal. Science 327:1657–1661

    Article  PubMed  CAS  Google Scholar 

  • Shakirov EV, Shippen DE (2004) Length regulation and dynamics of individual telomere tracts in wild-type Arabidopsis. Plant Cell 16:1959–1967

    Article  PubMed  CAS  Google Scholar 

  • Shakirov EV, Surovtseva YV, Osbun N, Shippen DE (2005) The Arabidopsis Pot1 and Pot2 proteins function in telomere length homeostasis and chromosome end protection. Mol Cell Biol 25:7725–7733

    Article  PubMed  CAS  Google Scholar 

  • Shampay J, Szostak JW, Blackburn EH (1984) DNA sequences of telomeres maintained in yeast. Nature 310:154–157

    Article  PubMed  CAS  Google Scholar 

  • Shay JW, Bacchetti S (1997) A survey of telomerase activity in human cancer. Eur J Cancer 33:787–791

    Article  PubMed  CAS  Google Scholar 

  • Shay JW, Pereira-Smith OM, Wright WE (1991) A role for both RB and p53 in the regulation of human cellular senescence. Exp Cell Res 196:33–39

    Article  PubMed  CAS  Google Scholar 

  • Shippen DE (2006) Plant telomeres. In: deLange T, Lundblad V, Blackburn EH (eds) Telomeres. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, p 525

    Google Scholar 

  • Singer MS, Gottschling DE (1994) TLC1: template RNA component of Saccharomyces cerevisiae telomerase. Science 266:404–409

    Article  PubMed  CAS  Google Scholar 

  • Smogorzewska A, van Steensel B, Bianchi A, Oelmann S, Schaefer MR, Schnapp G, de Lange T (2000) Control of human telomere length by TRF1 and TRF2. Mol Cell Biol 20:1659–1668

    Article  PubMed  CAS  Google Scholar 

  • Smogorzewska A, Karlseder J, Holtgreve-Grez H, Jauch A, de Lange T (2002) DNA ligase IV-dependent NHEJ of deprotected mammalian telomeres in G1 and G2. Curr Biol 12:1635–1644

    Article  PubMed  CAS  Google Scholar 

  • Snow BE, Erdmann N, Cruickshank J, Goldman H, Gill RM, Robinson MO, Harrington L (2003) Functional conservation of the telomerase protein Est1p in humans. Curr Biol 13:698–704

    Article  PubMed  CAS  Google Scholar 

  • Solovei I, Gaginskaya ER, Macgregor HC (1994) The arrangement and transcription of telomere DNA sequences at the ends of lampbrush chromosomes of birds. Chromosome Res 2:460–470

    Article  PubMed  CAS  Google Scholar 

  • Sugawara N (1989) DNA sequences at the telomeres of the fission yeast S. pombe. Ph.D. thesis, Harvard University, Cambridge, MA

    Google Scholar 

  • Surovtseva YV, Shakirov EV, Vespa L, Osbun N, Song X, Shippen DE (2007) Arabidopsis POT1 associates with the telomerase RNP and is required for telomere maintenance. EMBO J 26:3653–3661

    Article  PubMed  CAS  Google Scholar 

  • Szostak JW, Blackburn EH (1982) Cloning yeast telomeres on linear plasmid vectors. Cell 29:245–255

    Article  PubMed  CAS  Google Scholar 

  • Takai H, Smogorzewska A, de Lange T (2003) DNA damage foci at dysfunctional telomeres. Curr Biol 13:1549–1556

    Article  PubMed  CAS  Google Scholar 

  • Teixeira MT, Gilson E (2005) Telomere maintenance, function and evolution: the yeast paradigm. Chromosome Res 13:535–548

    Article  PubMed  CAS  Google Scholar 

  • Tomita K, Cooper JP (2008) Fission yeast Ccq1 is telomerase recruiter and local checkpoint controller. Genes Dev 22:3461–3474

    Article  PubMed  CAS  Google Scholar 

  • Tomita K, Matsuura A, Caspari T, Carr AM, Akamatsu Y, Iwasaki H, Mizuno K, Ohta K, Uritani M, Ushimaru T, Yoshinaga K, Ueno M (2003) Competition between the Rad50 complex and the Ku heterodimer reveals a role for Exo1 in processing double-strand breaks but not telomeres. Mol Cell Biol 23:5186–5197

    Article  PubMed  CAS  Google Scholar 

  • Torok T, Benitez C, Takacs S, Biessmann H (2007) The protein encoded by the gene proliferation disrupter (prod) is associated with the telomeric retrotransposon array in Drosophila melanogaster. Chromosoma 116:185–195

    Article  PubMed  CAS  Google Scholar 

  • Towbin BD, Meister P, Gasser SM (2009) The nuclear envelope-a scaffold for silencing? Curr Opin Genet Dev 19:180–186

    Article  PubMed  CAS  Google Scholar 

  • van Steensel B, de Lange T (1997) Control of telomere length by the human telomeric protein TRF1. Nature 385:740–743

    Article  PubMed  Google Scholar 

  • van Steensel B, Smogorzewska A, de Lange T (1998) TRF2 protects human telomeres from end-to-end fusions. Cell 92:401–413

    Article  PubMed  Google Scholar 

  • Vega LR, Mateyak MK, Zakian VA (2003) Getting to the end: telomerase access in yeast and humans. Nat Rev Mol Cell Biol 4:948–959

    Article  PubMed  CAS  Google Scholar 

  • Venteicher AS, Meng Z, Mason PJ, Veenstra TD, Artandi SE (2008) Identification of ATPases pontin and reptin as telomerase components essential for holoenzyme assembly. Cell 132:945–957

    Article  PubMed  CAS  Google Scholar 

  • Venteicher AS, Abreu EB, Meng Z, McCann KE, Terns RM, Veenstra TD, Terns MP, Artandi SE (2009) A human telomerase holoenzyme protein required for Cajal body localization and telomere synthesis. Science 323:644–648

    Article  PubMed  CAS  Google Scholar 

  • Vermaak D, Malik HS (2009) Multiple roles for heterochromatin protein 1 genes in Drosophila. Annu Rev Genet 43:467–492

    Article  PubMed  CAS  Google Scholar 

  • Wang SS, Zakian VA (1990) Sequencing of Saccharomyces telomeres cloned using T4 DNA polymerase reveals two domains. Mol Cell Biol 10:4415–4419

    PubMed  CAS  Google Scholar 

  • Wang RC, Smogorzewska A, de Lange T (2004) Homologous recombination generates T-loop-sized deletions at human telomeres. Cell 119:355–368

    Article  PubMed  CAS  Google Scholar 

  • Watson JD (1972) Origin of concatemeric T7 DNA. Nat New Biol 239:197–201

    Article  PubMed  CAS  Google Scholar 

  • Webb CJ, Zakian VA (2008) Identification and characterization of the Schizosaccharomyces pombe TER1 telomerase RNA. Nat Struct Mol Biol 15:34–42

    Article  PubMed  CAS  Google Scholar 

  • Wellinger RJ, Wolf AJ, Zakian VA (1993) Saccharomyces telomeres acquire single-strand TG1-3 tails late in S phase. Cell 72:51–60

    Article  PubMed  CAS  Google Scholar 

  • Yang SW, Kim SK, Kim WT (2004) Perturbation of NgTRF1 expression induces apoptosis-like cell death in tobacco BY-2 cells and implicates NgTRF1 in the control of telomere length and stability. Plant Cell 16:3370–3385

    Article  PubMed  CAS  Google Scholar 

  • Yao MC, Blackburn E, Gall JG (1979) Amplification of the rRNA genes in Tetrahymena. Cold Spring Harb Symp Quant Biol 43(Pt 2):1293–1296

    Article  PubMed  CAS  Google Scholar 

  • Yao MC, Blackburn E, Gall J (1981) Tandemly repeated C-C-C-C-A-A hexanucleotide of Tetrahymena rDNA is present elsewhere in the genome and may be related to the alteration of the somatic genome. J Cell Biol 90:515–520

    Article  PubMed  CAS  Google Scholar 

  • Ye JZ, Hockemeyer D, Krutchinsky AN, Loayza D, Hooper SM, Chait BT, de Lange T (2004) POT1-interacting protein PIP1: a telomere length regulator that recruits POT1 to the TIN2/TRF1 complex. Genes Dev 18:1649–1654

    Article  PubMed  CAS  Google Scholar 

  • Yehezkel S, Segev Y, Viegas-Pequignot E, Skorecki K, Selig S (2008) Hypomethylation of subtelomeric regions in ICF syndrome is associated with abnormally short telomeres and enhanced transcription from telomeric regions. Hum Mol Genet 17:2776–2789

    Article  PubMed  CAS  Google Scholar 

  • Zellinger B, Riha K (2007) Composition of plant telomeres. Biochim Biophys Acta 1769:399–409

    Article  PubMed  CAS  Google Scholar 

  • Zhang QS, Manche L, Xu RM, Krainer AR (2006) hnRNP A1 associates with telomere ends and stimulates telomerase activity. RNA 12:1116–1128

    Article  PubMed  CAS  Google Scholar 

  • Zhang LF, Ogawa Y, Ahn JY, Namekawa SH, Silva SS, Lee JT (2009) Telomeric RNAs mark sex chromosomes in stem cells. Genetics 182:685–698

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Harry Wischnewski for contributing to Fig. 4.2. We also thank Raghav Chawla and Amadou Bah for critical reading of the manuscript. CMA laboratory is supported by grants from ETHZ (ETH-15 08-1 and ETH-03 08-3), the Swiss National Science Foundation (3100A0-120090 and PP00P3-123356), the European Research Council (BFTERRA), and Fondazione Cariplo (2008-2507). CMCB is supported by a fellowship from Boehringer Ingelheim Fonds.

Author information

Authors and Affiliations

  1. Institute of Biochemistry, ETHZ-Eidgenössische Technische Hochschule Zürich, CH-8093, Zürich, Switzerland

    Rajika Arora, Catherine M. C. Brun & Claus M. Azzalin

Authors
  1. Rajika Arora
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Catherine M. C. Brun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Claus M. Azzalin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Claus M. Azzalin .

Editor information

Editors and Affiliations

  1. Center for Marine Research, Ruder Boskovic Institute, Bijenicka 54, Zagreb, 10001, Croatia

    Durdica Ugarkovic

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Arora, R., Brun, C.M.C., Azzalin, C.M. (2011). TERRA: Long Noncoding RNA at Eukaryotic Telomeres. In: Ugarkovic, D. (eds) Long Non-Coding RNAs. Progress in Molecular and Subcellular Biology(), vol 51. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-16502-3_4

Download citation

Publish with us

Policies and ethics

Search

Navigation