The Specificity and Flexibility of L1 Reverse Transcription Priming at Imperfect T-Tracts

English version České info

L1 retrotransposons have a prominent role in reshaping mammalian genomes. To replicate, the L1 ribonucleoprotein particle (RNP) first uses its endonuclease (EN) to nick the genomic DNA. The newly generated DNA end is subsequently used as a primer to initiate reverse transcription within the L1 RNA poly(A) tail, a process known as target-primed reverse transcription (TPRT). Prior studies demonstrated that most L1 insertions occur into sequences related to the L1 EN consensus sequence (degenerate 5′-TTTT/A-3′ sites) and frequently preceded by imperfect T-tracts. However, it is currently unclear whether—and to which degree—the liberated 3′-hydroxyl extremity on the genomic DNA needs to be accessible and complementary to the poly(A) tail of the L1 RNA for efficient priming of reverse transcription. Here, we employed a direct assay for the initiation of L1 reverse transcription to define the molecular rules that guide this process. First, efficient priming is detected with as few as 4 matching nucleotides at the primer 3′ end. Second, L1 RNP can tolerate terminal mismatches if they are compensated within the 10 last bases of the primer by an increased number of matching nucleotides. All terminal mismatches are not equally detrimental to DNA extension, a C being extended at higher levels than an A or a G. Third, efficient priming in the context of duplex DNA requires a 3′ overhang. This suggests the possible existence of additional DNA processing steps, which generate a single-stranded 3′ end to allow L1 reverse transcription. Based on these data we propose that the specificity of L1 reverse transcription initiation contributes, together with the specificity of the initial EN cleavage, to the distribution of new L1 insertions within the human genome.

Vyšlo v časopise: The Specificity and Flexibility of L1 Reverse Transcription Priming at Imperfect T-Tracts. PLoS Genet 9(5): e32767. doi:10.1371/journal.pgen.1003499
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003499

Souhrn

Zdroje

1. LanderES, LintonLM, BirrenB, NusbaumC, ZodyMC, et al. (2001) Initial sequencing and analysis of the human genome. Nature 409: 860–921.

2. GoodierJL, KazazianHH (2008) Retrotransposons revisited: the restraint and rehabilitation of parasites. Cell 135: 23–35.

3. BelancioVP, HedgesDJ, DeiningerP (2008) Mammalian non-LTR retrotransposons: for better or worse, in sickness and in health. Genome Res 18: 343–358.

4. CordauxR, BatzerMA (2009) The impact of retrotransposons on human genome evolution. Nat Rev Genet 10: 691–703.

5. O'DonnellKA, BurnsKH (2010) Mobilizing diversity: transposable element insertions in genetic variation and disease. Mob DNA 1: 21.

6. BeckCR, Garcia-PerezJL, BadgeRM, MoranJV (2011) LINE-1 Elements in Structural Variation and Disease. Annu Rev Genomics Hum Genet 12: 187–215.

7. SwergoldGD (1990) Identification, characterization, and cell specificity of a human LINE-1 promoter. Mol Cell Biol 10: 6718–6729.

8. EsnaultC, MaestreJ, HeidmannT (2000) Human LINE retrotransposons generate processed pseudogenes. Nat Genet 24: 363–367.

9. WeiW, GilbertN, OoiSL, LawlerJF, OstertagEM, et al. (2001) Human L1 retrotransposition: cis preference versus trans complementation. Mol Cell Biol 21: 1429–1439.

10. KulpaDA, MoranJV (2006) Cis-preferential LINE-1 reverse transcriptase activity in ribonucleoprotein particles. Nat Struct Mol Biol 13: 655–660.

11. AlischRS, Garcia-PerezJL, MuotriAR, GageFH, MoranJV (2006) Unconventional translation of mammalian LINE-1 retrotransposons. Genes Dev 20: 210–224.

12. MartinSL (1991) Ribonucleoprotein particles with LINE-1 RNA in mouse embryonal carcinoma cells. Mol Cell Biol 11: 4804–4807.

13. HohjohH, SingerMF (1996) Cytoplasmic ribonucleoprotein complexes containing human LINE-1 protein and RNA. EMBO J 15: 630–639.

14. KoloshaVO, MartinSL (1997) In vitro properties of the first ORF protein from mouse LINE-1 support its role in ribonucleoprotein particle formation during retrotransposition. Proc Natl Acad Sci U S A 94: 10155–10160.

15. GoodierJL, OstertagEM, EnglekaKA, SelemeMC, KazazianHH (2004) A potential role for the nucleolus in L1 retrotransposition. Hum Mol Genet 13: 1041–1048.

16. KulpaDA, MoranJV (2005) Ribonucleoprotein particle formation is necessary but not sufficient for LINE-1 retrotransposition. Hum Mol Genet 14: 3237–3248.

17. GoodierJL, ZhangL, VetterMR, KazazianHH (2007) LINE-1 ORF1 protein localizes in stress granules with other RNA-binding proteins, including components of RNA interference RNA-induced silencing complex. Mol Cell Biol 27: 6469–6483.

18. DoucetAJ, HulmeAE, SahinovicE, KulpaDA, MoldovanJB, et al. (2010) Characterization of LINE-1 ribonucleoprotein particles. PLoS Genet 6: e1001150 doi:10.1371/journal.pgen.1001150.

19. GoodierJL, MandalPK, ZhangL, KazazianHH (2010) Discrete subcellular partitioning of human retrotransposon RNAs despite a common mechanism of genome insertion. Hum Mol Genet 19: 1712–1725.

20. MartinSL, BushmanFD (2001) Nucleic acid chaperone activity of the ORF1 protein from the mouse LINE-1 retrotransposon. Mol Cell Biol 21: 467–475.

21. KoloshaVO, MartinSL (2003) High-affinity, non-sequence-specific RNA binding by the open reading frame 1 (ORF1) protein from long interspersed nuclear element 1 (LINE-1). J Biol Chem 278: 8112–8117.

22. MartinSL, BranciforteD, KellerD, BainDL (2003) Trimeric structure for an essential protein in L1 retrotransposition. Proc Natl Acad Sci U S A 100: 13815–13820.

23. BasameS, Wai-lun LiP, HowardG, BranciforteD, KellerD, MartinSL (2006) Spatial assembly and RNA binding stoichiometry of a LINE-1 protein essential for retrotransposition. J Mol Biol 357: 351–357.

24. MartinSL (2010) Nucleic acid chaperone properties of ORF1p from the non-LTR retrotransposon, LINE-1. RNA Biol 7: 67–72.

25. KhazinaE, TruffaultV, BüttnerR, SchmidtS, ColesM, WeichenriederO (2011) Trimeric structure and flexibility of the L1ORF1 protein in human L1 retrotransposition. Nat Struct Mol Biol 18: 1006–1014.

26. MathiasSL, ScottAF, KazazianHH, BoekeJD, GabrielA (1991) Reverse transcriptase encoded by a human transposable element. Science 254: 1808–1810.

27. FengQ, MoranJV, KazazianHH, BoekeJD (1996) Human L1 retrotransposon encodes a conserved endonuclease required for retrotransposition. Cell 87: 905–916.

28. MoranJV, HolmesSE, NaasTP, DeBerardinisRJ, BoekeJD, KazazianHH (1996) High frequency retrotransposition in cultured mammalian cells. Cell 87: 917–927.

29. MartinSL, CruceanuM, BranciforteD, Wai-Lun LiP, KwokSC, et al. (2005) LINE-1 retrotransposition requires the nucleic acid chaperone activity of the ORF1 protein. J Mol Biol 348: 549–561.

30. KuboS, SelemeMC, SoiferHS, PerezJL, MoranJV, et al. (2006) L1 retrotransposition in nondividing and primary human somatic cells. Proc Natl Acad Sci U S A 103: 8036–8041.

31. LuanDD, KormanMH, JakubczakJL, EickbushTH (1993) Reverse transcription of R2Bm RNA is primed by a nick at the chromosomal target site: a mechanism for non-LTR retrotransposition. Cell 72: 595–605.

32. XiongYE, EickbushTH (1988) Functional expression of a sequence-specific endonuclease encoded by the retrotransposon R2Bm. Cell 55: 235–246.

33. CostGJ, FengQ, JacquierA, BoekeJD (2002) Human L1 element target-primed reverse transcription in vitro. EMBO J 21: 5899–5910.

34. ChristensenSM, YeJ, EickbushTH (2006) RNA from the 5′ end of the R2 retrotransposon controls R2 protein binding to and cleavage of its DNA target site. Proc Natl Acad Sci U S A 103: 17602–17607.

35. EickbushTH, JamburuthugodaVK (2008) The diversity of retrotransposons and the properties of their reverse transcriptases. Virus Res 134: 221–234.

36. LuanDD, EickbushTH (1995) RNA template requirements for target DNA-primed reverse transcription by the R2 retrotransposable element. Mol Cell Biol 15: 3882–3891.

37. LuanDD, EickbushTH (1996) Downstream 28S gene sequences on the RNA template affect the choice of primer and the accuracy of initiation by the R2 reverse transcriptase. Mol Cell Biol 16: 4726–4734.

38. MalikHS, BurkeWD, EickbushTH (1999) The age and evolution of non-LTR retrotransposable elements. Mol Biol Evol 16: 793–805.

39. KajikawaM, OkadaN (2002) LINEs mobilize SINEs in the eel through a shared 3′ sequence. Cell 111: 433–444.

40. OsanaiM, TakahashiH, KojimaKK, HamadaM, FujiwaraH (2004) Essential motifs in the 3′ untranslated region required for retrotransposition and the precise start of reverse transcription in non-long-terminal-repeat retrotransposon SART1. Mol Cell Biol 24: 7902–7913.

41. AnzaiT, OsanaiM, HamadaM, FujiwaraH (2005) Functional roles of 3′-terminal structures of template RNA during in vivo retrotransposition of non-LTR retrotransposon, R1Bm. Nucleic Acids Res 33: 1993–2002.

42. IchiyanagiK, NakajimaR, KajikawaM, OkadaN (2007) Novel retrotransposon analysis reveals multiple mobility pathways dictated by hosts. Genome Res 17: 33–41.

43. DongC, PoulterRT, HanJS (2009) LINE-like retrotransposition in Saccharomyces cerevisiae. Genetics 181: 301–311.

44. CostGJ, BoekeJD (1998) Targeting of human retrotransposon integration is directed by the specificity of the L1 endonuclease for regions of unusual DNA structure. Biochemistry 37: 18081–18093.

45. OstertagEM, KazazianHH (2001) Twin priming: a proposed mechanism for the creation of inversions in L1 retrotransposition. Genome Res 11: 2059–2065.

46. GilbertN, Lutz-PriggeS, MoranJV (2002) Genomic deletions created upon LINE-1 retrotransposition. Cell 110: 315–325.

47. SymerDE, ConnellyC, SzakST, CaputoEM, CostGJ, et al. (2002) Human l1 retrotransposition is associated with genetic instability in vivo. Cell 110: 327–338.

48. SzakST, PickeralOK, MakalowskiW, BoguskiMS, LandsmanD, BoekeJD (2002) Molecular archeology of L1 insertions in the human genome. Genome Biol 3: research0052.

49. GilbertN, LutzS, MorrishTA, MoranJV (2005) Multiple fates of L1 retrotransposition intermediates in cultured human cells. Mol Cell Biol 25: 7780–7795.

50. GasiorSL, PrestonG, HedgesDJ, GilbertN, MoranJV, DeiningerPL (2007) Characterization of pre-insertion loci of de novo L1 insertions. Gene 390: 190–198.

51. KoperaHC, MoldovanJB, MorrishTA, Garcia-PerezJL, MoranJV (2011) Similarities between long interspersed element-1 (LINE-1) reverse transcriptase and telomerase. Proc Natl Acad Sci U S A 108: 20345–20350.

52. HanJS, BoekeJD (2004) A highly active synthetic mammalian retrotransposon. Nature 429: 314–318.

53. JonesRB, GarrisonKE, WongJC, DuanEH, NixonDF, OstrowskiMA (2008) Nucleoside analogue reverse transcriptase inhibitors differentially inhibit human LINE-1 retrotransposition. PLoS ONE 3: e1547 doi:10.1371/journal.pone.0001547.

54. KroutterEN, BelancioVP, WagstaffBJ, Roy-EngelAM (2009) The RNA polymerase dictates ORF1 requirement and timing of LINE and SINE retrotransposition. PLoS Genet 5: e1000458 doi: 10.1371/journal.pgen.1000458.

55. DaiL, HuangQ, BoekeJD (2011) Effect of reverse transcriptase inhibitors on LINE-1 and Ty1 reverse transcriptase activities and on LINE-1 retrotransposition. BMC Biochem 12: 18.

56. WagstaffBJ, HedgesDJ, DerbesRS, Campos SanchezR, ChiaromonteF, et al. (2012) Rescuing Alu: Recovery of New Inserts Shows LINE-1 Preserves Alu Activity through A-Tail Expansion. PLoS Genet 8: e1002842 doi:10.1371/journal.pgen.1002842.

57. BibilloA, EickbushTH (2002) High processivity of the reverse transcriptase from a non-long terminal repeat retrotransposon. J Biol Chem 277: 34836–34845.

58. JamburuthugodaVK, EickbushTH (2011) The reverse transcriptase encoded by the non-LTR retrotransposon R2 is as error-prone as that encoded by HIV-1. J Mol Biol 407: 661–672.

59. WangJ, SongL, GroverD, AzrakS, BatzerMA, LiangP (2006) dbRIP: a highly integrated database of retrotransposon insertion polymorphisms in humans. Hum Mutat 27: 323–329.

60. LeeE, IskowR, YangL, GokcumenO, HaseleyP, et al. (2012) Landscape of somatic retrotransposition in human cancers. Science 337: 967–971.

61. SolyomS, EwingAD, RahrmannEP, DoucetT, NelsonHH, et al. (2012) Extensive somatic L1 retrotransposition in colorectal tumors. Genome Res 22: 2328–2338.

62. AkagiK, LiJ, StephensRM, VolfovskyN, SymerDE (2008) Extensive variation between inbred mouse strains due to endogenous L1 retrotransposition. Genome Res 18: 869–880.

63. EwingAD, KazazianHH (2010) High-throughput sequencing reveals extensive variation in human-specific L1 content in individual human genomes. Genome Res 20: 1262–1270.

64. BeckCR, CollierP, MacfarlaneC, MaligM, KiddJM, et al. (2010) LINE-1 Retrotransposition Activity in Human Genomes. Cell 141: 1159–1170.

65. HuangCR, SchneiderAM, LuY, NiranjanT, ShenP, et al. (2010) Mobile interspersed repeats are major structural variants in the human genome. Cell 141: 1171–1182.

66. IskowRC, McCabeMT, MillsRE, ToreneS, PittardWS, et al. (2010) Natural mutagenesis of human genomes by endogenous retrotransposons. Cell 141: 1253–1261.

67. PiskarevaO, SchmatchenkoV (2006) DNA polymerization by the reverse transcriptase of the human L1 retrotransposon on its own template in vitro. FEBS Lett 580: 661–668.

68. MorrishTA, GilbertN, MyersJS, VincentBJ, StamatoTD, et al. (2002) DNA repair mediated by endonuclease-independent LINE-1 retrotransposition. Nat Genet 31: 159–165.

69. MorrishTA, Garcia-PerezJL, StamatoTD, TaccioliGE, SekiguchiJ, MoranJV (2007) Endonuclease-independent LINE-1 retrotransposition at mammalian telomeres. Nature 446: 208–212.

70. SenSK, HuangCT, HanK, BatzerMA (2007) Endonuclease-independent insertion provides an alternative pathway for L1 retrotransposition in the human genome. Nucleic Acids Res 35: 3741–3751.

71. PickeralOK, MakałowskiW, BoguskiMS, BoekeJD (2000) Frequent human genomic DNA transduction driven by LINE-1 retrotransposition. Genome Res 10: 411–415.

72. GoodierJL, OstertagEM, KazazianHH (2000) Transduction of 3′-flanking sequences is common in L1 retrotransposition. Hum Mol Genet 9: 653–657.

73. RepanasK, ZinglerN, LayerLE, SchumannGG, PerrakisA, WeichenriederO (2007) Determinants for DNA target structure selectivity of the human LINE-1 retrotransposon endonuclease. Nucleic Acids Res 35: 4914–4926.

74. BibilloA, EickbushTH (2004) End-to-end template jumping by the reverse transcriptase encoded by the R2 retrotransposon. J Biol Chem 279: 14945–14953.

75. BelgnaouiSM, GosdenRG, SemmesOJ, HaoudiA (2006) Human LINE-1 retrotransposon induces DNA damage and apoptosis in cancer cells. Cancer Cell Int 6: 13.

76. GasiorSL, WakemanTP, XuB, DeiningerPL (2006) The human LINE-1 retrotransposon creates DNA double-strand breaks. J Mol Biol 357: 1383–1393.

77. CristofariG, GabusC, FicheuxD, BonaM, Le GriceSF, DarlixJL (1999) Characterization of active reverse transcriptase and nucleoprotein complexes of the yeast retrotransposon Ty3 in vitro. J Biol Chem 274: 36643–36648.

78. CristofariG, FicheuxD, DarlixJL (2000) The GAG-like protein of the yeast Ty1 retrotransposon contains a nucleic acid chaperone domain analogous to retroviral nucleocapsid proteins. J Biol Chem 275: 19210–19217.

79. CristofariG, BampiC, WilhelmM, WilhelmFX, DarlixJL (2002) A 5′-3′ long-range interaction in Ty1 RNA controls its reverse transcription and retrotransposition. EMBO J 21: 4368–4379.

80. CristofariG, DarlixJL (2002) The ubiquitous nature of RNA chaperone proteins. Prog Nucleic Acid Res Mol Biol 72: 223–268.

81. KassEM, JasinM (2010) Collaboration and competition between DNA double-strand break repair pathways. FEBS Lett 584: 3703–3708.

82. MakarovVL, HiroseY, LangmoreJP (1997) Long G tails at both ends of human chromosomes suggest a C strand degradation mechanism for telomere shortening. Cell 88: 657–666.

83. McElligottR, WellingerRJ (1997) The terminal DNA structure of mammalian chromosomes. EMBO J 16: 3705–3714.

84. WuP, TakaiH, de LangeT (2012) Telomeric 3′ Overhangs Derive from Resection by Exo1 and Apollo and Fill-In by POT1b-Associated CST. Cell 150: 39–52.

85. GreiderCW, BlackburnEH (1987) The telomere terminal transferase of Tetrahymena is a ribonucleoprotein enzyme with two kinds of primer specificity. Cell 51: 887–898.

86. LingnerJ, HughesTR, ShevchenkoA, MannM, LundbladV, CechTR (1997) Reverse transcriptase motifs in the catalytic subunit of telomerase. Science 276: 561–567.

87. LingnerJ, CechTR (1996) Purification of telomerase from Euplotes aediculatus: requirement of a primer 3′ overhang. Proc Natl Acad Sci U S A 93: 10712–10717.

88. EickbushTH (1997) Telomerase and retrotransposons: which came first? Science 277: 911–912.

89. NakamuraTM, CechTR (1998) Reversing time: origin of telomerase. Cell 92: 587–590.

90. GladyshevEA, ArkhipovaIR (2007) Telomere-associated endonuclease-deficient Penelope-like retroelements in diverse eukaryotes. Proc Natl Acad Sci U S A 104: 9352–9357.

91. AnW, DavisES, ThompsonTL, O'DonnellKA, LeeCY, BoekeJD (2009) Plug and play modular strategies for synthetic retrotransposons. Methods 49: 227–235.