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Transposable elements and G-quadruplexes

Abstract

A significant part of eukaryotic genomes is formed by transposable elements (TEs) containing not only genes but also regulatory sequences. Some of the regulatory sequences located within TEs can form secondary structures like hairpins or three-stranded (triplex DNA) and four-stranded (quadruplex DNA) conformations. This review focuses on recent evidence showing that G-quadruplex-forming sequences in particular are often present in specific parts of TEs in plants and humans. We discuss the potential role of these structures in the TE life cycle as well as the impact of G-quadruplexes on replication, transcription, translation, chromatin status, and recombination. The aim of this review is to emphasize that TEs may serve as vehicles for the genomic spread of G-quadruplexes. These non-canonical DNA structures and their conformational switches may constitute another regulatory system that, together with small and long non-coding RNA molecules and proteins, contribute to the complex cellular network resulting in the large diversity of eukaryotes.

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Abbreviations

TEs:

Transposable elements

LTR:

Long terminal repeat

PQS:

Potential quadruplex-forming sequence

References

  1. Abad JP, Villasante A (1999) The 3′ non-coding region of the Drosophila melanogaster HeT-A telomeric retrotransposon contains sequences with propensity to form G-quadruplex DNA. FEBS Lett 453:59–62

    CAS  Article  PubMed  Google Scholar 

  2. Barrett LW, Fletcher S, Wilton SD (2012) Regulation of eukaryotic gene expression by the untranslated gene regions and other non-coding elements. Cell Mol Life Sci 69:3613–3634

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  3. Beaudoin J-D, Perreault J-P (2013) Exploring mRNA 3′-UTR G-quadruplexes: evidence of roles in both alternative polyadenylation and mRNA shortening. Nucleic Acids Res 41:5898–5911

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  4. Biémont C, Vieira C (2006) Genetics: junk DNA as an evolutionary force. Nature 443:521–524

    Article  PubMed  Google Scholar 

  5. Boán F, Gómez-Márquez J (2010) In vitro recombination mediated by G-quadruplexes. Chembiochem: Eur J Chem Biol 11:331–334

    Article  Google Scholar 

  6. Bochman ML, Paeschke K, Zakian VA (2012) DNA secondary structures: stability and function of G-quadruplex structures. Nat Rev Genet 13:770–780

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  7. Bohr VA (2008) Rising from the RecQ-age: the role of human RecQ helicases in genome maintenance. Trends Biochem Sci 33:609–620

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  8. Bousios A, Darzentas N, Tsaftaris A, Pearce SR (2010) Highly conserved motifs in non-coding regions of Sirevirus retrotransposons: the key for their pattern of distribution within and across plants? BMC Genomics 11:89

    PubMed Central  Article  PubMed  Google Scholar 

  9. Brázda V, Hároníková L, Liao JCC, Fojta M (2014) DNA and RNA quadruplex-binding proteins. Int J Mol Sci 15:17493–17517

    PubMed Central  Article  PubMed  Google Scholar 

  10. Brown JA, Bulkley D, Wang J et al (2014) Structural insights into the stabilization of MALAT1 noncoding RNA by a bipartite triple helix. Nat Struct Mol Biol 21:633–640

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  11. Broxson C, Beckett J, Tornaletti S (2011) Transcription arrest by a G quadruplex forming-trinucleotide repeat sequence from the human c-myb gene. Biochemistry 50:4162–4172

    CAS  Article  PubMed  Google Scholar 

  12. Bureau TE, Wessler SR (1992) Tourist: a large family of small inverted repeat elements frequently associated with maize genes. Plant Cell 4:1283–1294

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  13. Cerofolini L, Amato J, Giachetti A, Limongelli V, Novellino E, Parrinello M et al (2014) G-triplex structure and formation propensity. Nucleic Acids Res 42:13393–13404

    PubMed Central  Article  PubMed  Google Scholar 

  14. Chen L, Dahlstrom JE, Lee S-H, Rangasamy D (2012) Naturally occurring endo-siRNA silences LINE-1 retrotransposons in human cells through DNA methylation. Epigenetics 7:758–771

    CAS  Article  PubMed  Google Scholar 

  15. Cui F, Sirotin MV, Zhurkin VB (2011) Impact of Alu repeats on the evolution of human p53 binding sites. Biol Direct 6:2

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  16. Dai J, Carver M, Punchihewa C, Jones RA, Yang D (2007) Structure of the Hybrid-2 type intramolecular human telomeric G-quadruplex in K+ solution: insights into structure polymorphism of the human telomeric sequence. Nucleic Acids Res 35:4927–4940

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  17. Downs JA, Jackson SP (1999) Involvement of DNA end-binding protein Ku in Ty element retrotransposition. Mol Cell Biol 19:6260–6268

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  18. Guerrero-Bosagna C, Weeks S, Skinner MK (2014) Identification of genomic features in environmentally induced epigenetic transgenerational inherited sperm epimutations. PLoS ONE 9, e100194

    PubMed Central  Article  PubMed  Google Scholar 

  19. Han JS (2010) Non-long terminal repeat (non-LTR) retrotransposons: mechanisms, recent developments, and unanswered questions. Mob DNA 1:15

    PubMed Central  Article  PubMed  Google Scholar 

  20. Hangauer MJ, Vaughn IW, McManus MT (2013) Pervasive transcription of the human genome produces thousands of previously unidentified long intergenic noncoding RNAs. PLoS Genet 9, e1003569

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  21. Hegyi H (2015) Enhancer-promoter interaction facilitated by transiently forming G-quadruplexes. Sci Rep 5:9165

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  22. Howell R, Usdin K (1997) The ability to form intrastrand tetraplexes is an evolutionarily conserved feature of the 3′ end of L1 retrotransposons. Mol Biol Evol 14:144–155

    CAS  Article  PubMed  Google Scholar 

  23. Huda A, Bowen NJ, Conley AB, Jordan IK (2011a) Epigenetic regulation of transposable element derived human gene promoters. Gene 475:39–48

    CAS  Article  PubMed  Google Scholar 

  24. Huda A, Tyagi E, Mariño-Ramírez L et al (2011b) Prediction of transposable element derived enhancers using chromatin modification profiles. PLoS ONE 6, e27513

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  25. Huppert JL, Balasubramanian S (2007) G-quadruplexes in promoters throughout the human genome. Nucleic Acids Res 35:406–413

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  26. Jayaraj GG, Pandey S, Scaria V, Maiti S (2012) Potential G-quadruplexes in the human long non-coding transcriptome. RNA Biol 9:81–86

    CAS  Article  PubMed  Google Scholar 

  27. Kapitonov VV, Jurka J (2005) RAG1 core and V(D)J recombination signal sequences were derived from transib transposons. PLoS Biol 3, e181

    PubMed Central  Article  PubMed  Google Scholar 

  28. Kapusta A, Kronenberg Z, Lynch VJ et al (2013) Transposable elements are major contributors to the origin, diversification, and regulation of vertebrate long noncoding RNAs. PLoS Genet 9, e1003470

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  29. Kejnovská I, Tůmová M, Vorlícková M (2001) (CGA)(4): parallel, anti-parallel, right-handed and left-handed homoduplexes of a trinucleotide repeat DNA. Biochim Biophys Acta 1527:73–80

    Article  PubMed  Google Scholar 

  30. Kejnovsky E, Lexa M (2014) Quadruplex-forming DNA sequences spread by retrotransposons may serve as genome regulators. Mobile Genet Elem 4, e28084

    Article  Google Scholar 

  31. Kejnovský E, Michalovova M, Steflova P et al (2013) Expansion of microsatellites on evolutionary young Y chromosome. PLoS ONE 8, e45519

    PubMed Central  Article  PubMed  Google Scholar 

  32. Lawrence DC, Stover CC, Noznitsky J et al (2003) Structure of the intact stem and bulge of HIV-1 Psi-RNA stem-loop SL1. J Mol Biol 326:529–542

    CAS  Article  PubMed  Google Scholar 

  33. Lever A, Gottlinger H, Haseltine W, Sodroski J (1989) Identification of a sequence required for efficient packaging of human immunodeficiency virus type 1 RNA into virions. J Virol 63:4085–4087

    PubMed Central  CAS  PubMed  Google Scholar 

  34. Lexa M, Kejnovský E, Steflová P et al (2014a) Quadruplex-forming sequences occupy discrete regions inside plant LTR retrotransposons. Nucleic Acids Res 42:968–978

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  35. Lexa M, Steflova P, Martinek T et al (2014b) Guanine quadruplexes are formed by specific regions of human transposable elements. BMC Genomics 15:1032

    PubMed Central  Article  PubMed  Google Scholar 

  36. Liu S, Yeh C-T, Ji T et al (2009) Mu transposon insertion sites and meiotic recombination events co-localize with epigenetic marks for open chromatin across the maize genome. PLoS Genet 5, e1000733

    PubMed Central  Article  PubMed  Google Scholar 

  37. Macas J, Koblízková A, Navrátilová A, Neumann P (2009) Hypervariable 3′ UTR region of plant LTR-retrotransposons as a source of novel satellite repeats. Gene 448:198–206

    CAS  Article  PubMed  Google Scholar 

  38. McCue AD, Nuthikattu S, Slotkin RK (2013) Genome-wide identification of genes regulated in trans by transposable element small interfering RNAs. RNA Biol 10:1379–1395

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  39. Millevoi S, Moine H, Vagner S (2012) G-quadruplexes in RNA biology. WIRES 3:495–507

    CAS  Article  Google Scholar 

  40. Morris MJ, Negishi Y, Pazsint C et al (2010) An RNA G-quadruplex is essential for cap-independent translation initiation in human VEGF IRES. J Am Chem Soc 132:17831–17839

    CAS  Article  PubMed  Google Scholar 

  41. Nadir E, Margalit H, Gallily T, Ben-Sasson SA (1996) Microsatellite spreading in the human genome: evolutionary mechanisms and structural implications. Proc Natl Acad Sci U S A 93:6470–6475

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  42. Nambiar M, Goldsmith G, Moorthy BT et al (2011) Formation of a G-quadruplex at the BCL2 major breakpoint region of the t(14;18) translocation in follicular lymphoma. Nucleic Acids Res 39:936–948

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  43. Paramasivam M, Membrino A, Cogoi S et al (2009) Protein hnRNP A1 and its derivative Up1 unfold quadruplex DNA in the human KRAS promoter: implications for transcription. Nucleic Acids Res 37:2841–2853

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  44. Pearson CE, Sinden RR (1998) Trinucleotide repeat DNA structures: dynamic mutations from dynamic DNA. Curr Opin Struct Biol 8:321–330

    CAS  Article  PubMed  Google Scholar 

  45. Pezic D, Manakov SA, Sachidanandam R, Aravin AA (2014) piRNA pathway targets active LINE1 elements to establish the repressive H3K9me3 mark in germ cells. Genes Dev 28:1410–1428

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  46. Piekna-Przybylska D, Sullivan MA, Sharma G, Bambara RA (2014) U3 region in the HIV-1 genome adopts a G-quadruplex structure in its RNA and DNA sequence. Biochemistry 53:2581–2593

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  47. Piriyapongsa J, Jordan IK (2008) Dual coding of siRNAs and miRNAs by plant transposable elements. RNA 14:814–821

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  48. Quante T, Otto B, Brázdová M et al (2012) Mutant p53 is a transcriptional co-factor that binds to G-rich regulatory regions of active genes and generates transcriptional plasticity. Cell Cycle 11:3290–3303

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  49. Rajendran A, Endo M, Hidaka K, Sugiyama H (2014) Direct and single-molecule visualization of the solution-state structures of G-hairpin and G-triplex intermediates. Angew Chem Int Ed 53:4107–4112

    CAS  Article  Google Scholar 

  50. Rich A (1993) DNA comes in many forms. Gene 135:99–109

    CAS  Article  PubMed  Google Scholar 

  51. Sabot F, Schulman AH (2006) Parasitism and the retrotransposon life cycle in plants: a hitchhiker’s guide to the genome. Heredity 97:381–388

    CAS  Article  PubMed  Google Scholar 

  52. Sanders CM (2010) Human Pif1 helicase is a G-quadruplex DNA-binding protein with G-quadruplex DNA-unwinding activity. Biochem J 430:119–128

    CAS  Article  PubMed  Google Scholar 

  53. Savage AL, Bubb VJ, Breen G, Quinn JP (2013) Characterisation of the potential function of SVA retrotransposons to modulate gene expression patterns. BMC Evol Biol 13:101

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  54. Schwarzbauer K, Bodenhofer U, Hochreiter S (2012) Genome-wide chromatin remodeling identified at GC-rich long nucleosome-free regions. PLoS ONE 7, e47924

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  55. Smestad J, Maher L (2015) Putative G-quadruplex forming sequence signatures in genes differentially transcribed upon loss of BLM or WRN helicases. BioRxiv. doi:10.1101/013664

    Google Scholar 

  56. Steinbauerová V, Neumann P, Novák P, Macas J (2011) A widespread occurrence of extra open reading frames in plant Ty3/gypsy retrotransposons. Genetica 139:1543–1555

    Article  PubMed  Google Scholar 

  57. Sundquist WI, Heaphy S (1993) Evidence for interstrand quadruplex formation in the dimerization of human immunodeficiency virus 1 genomic RNA. Proc Natl Acad Sci U S A 90:3393–3397

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  58. Szak ST, Pickeral OK, Makalowski W et al (2002) Molecular archeology of L1 insertions in the human genome. Genome Biol 3, research0052

    PubMed Central  Article  PubMed  Google Scholar 

  59. Tlučková K, Marušič M, Tóthová P et al (2013) Human papillomavirus G-quadruplexes. Biochemistry 52:7207–7216

    Article  PubMed  Google Scholar 

  60. Vicient C, Suoniemi A, Anamthawat-Jónsson K et al (1999) Retrotransposon BARE-1 and its role in genome evolution in the genus Hordeum. Plant Cell 11:1769–1784

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  61. Volff J-N (2006) Turning junk into gold: domestication of transposable elements and the creation of new genes in eukaryotes. BioEssays 28:913–922

    CAS  Article  PubMed  Google Scholar 

  62. Watson JD, Crick FHC (2003) A structure for deoxyribose nucleic acid. 1953. Nature 421:397–398

    CAS  PubMed  Google Scholar 

  63. Whitehouse I, Owen-Hughes T (2010) ATRX: Put me on repeat. Cell 143:335–336

    CAS  Article  PubMed  Google Scholar 

  64. Wicker T, Sabot F, Hua-Van A et al (2007) A unified classification system for eukaryotic transposable elements. Nat Rev Genet 8:973–982

    CAS  Article  PubMed  Google Scholar 

  65. Wong HM, Huppert JL (2009) Stable G-quadruplexes are found outside nucleosome-bound regions. Mol BioSyst 5:1713–1719

    CAS  Article  PubMed  Google Scholar 

  66. Wu Y, Shin-ya K, Brosh RM (2008) FANCJ helicase defective in Fanconia anemia and breast cancer unwinds G-quadruplex DNA to defend genomic stability. Mol Cell Biol 28:4116–4128

    PubMed Central  CAS  Article  PubMed  Google Scholar 

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Acknowledgments

This research was supported by the Czech Science Foundation (grant 15-02891S). We would like to thank Professor Boris Vyskot for a critical reading of this manuscript.

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Correspondence to Eduard Kejnovsky.

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Responsible Editors: Maria Assunta Biscotti, Pat Heslop-Harrison and Ettore Olmo

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Kejnovsky, E., Tokan, V. & Lexa, M. Transposable elements and G-quadruplexes. Chromosome Res 23, 615–623 (2015). https://doi.org/10.1007/s10577-015-9491-7

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Keywords

  • transposable elements
  • LTR retrotransposons
  • DNA and RNA quadruplexes
  • G-quadruplexes
  • transcription
  • recombination
  • replication