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Vol. 110, No. 1-4, 2005
Issue release date: 2005
Cytogenet Genome Res 110:269–287 (2005)
(DOI:10.1159/000084960)

Reverse transcriptase and integrase of the Saccharomyces cerevisiae Ty1 element

Wilhelm F.-X. · Wilhelm M. · Gabriel A.
aInstitut de Biologie Moleculaire et Cellulaire, Strasbourg (France); bDepartment of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ (USA)

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Abstract

Integrase (IN) and reverse transcriptase (RT) play a central role in transposition of retroelements. The mechanism of integration by IN and the steps of the replication process mediated by RT are briefly described here. Recently, active recombinant forms of Ty1 IN and RT have been obtained. This has allowed a more detailed understanding of their biochemical and structural properties and has made possible combined in vitro and in vivo analyses of their functions. A focus of this review is to discuss some of the results obtained thus far with these two recombinant proteins and to propose future directions.    



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References

  1. Adams SE, Mellor J, Gull K, Sim RB, Tuite MF, Kingsman SM, Kingsman AJ: The functions and relationships of Ty-VLP proteins in yeast reflects those of mammalian retroviral proteins. Cell 49:111–119 (1987).
  2. AlKhayat HA, Bhella D, Kenney JM, Roth JF, Kingsman AJ, Martin-Rendon E, Saibil HR: Yeast Ty retrotransposons assemble into virus-like particles whose T-numbers depend on the C-terminal length of the capsid protein. J Mol Biol 292:65–73 (1999).
  3. Arts EJ, Le Grice SF: Interaction of retroviral reverse transcriptase with template-primer duplexes during replication. Prog Nucleic Acid Res Mol Biol 58:339–393 (1998).
  4. Barat C, Lullien V, Schatz O, Keith G, Nugeyre MT, Grüninger-Leitch F, Barré-Sinoussi F, Le Grice SF, Darlix JL: HIV-1 reverse transcriptase specifically interacts with the anticodon domain of its cognate primer tRNA. EMBO J 8:3279–3285 (1989).
  5. Belcourt MF, Farabaugh PJ: Ribosomal frameshifting in the yeast retrotransposon Ty: tRNA induce slippage on a 7 nucleotides minimal site. Cell 62:339–352 (1990).
  6. Blum HE, Harris JD, Ventura P, Walker D, Staskus K, Retzel E, Haase AT: Synthesis in cell culture of the gapped linear duplex DNA of the slow virus visna. Virology 142:270–277 (1985).
  7. Boeke JD, Sandmeyer S: Yeast transposable elements, in Broach JR, Jones EW, Pringle J (eds): The Molecular and Cellular Biology of the Yeast Saccharomyces cerevisiae, pp 193–261 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY 1991).
  8. Boeke JD, Stoye JP: Retrotransposons, endogenous retroviruses and the evolution of retroelements, in Coffin JM, Hughes SH, Varmus HE (eds): Retroviruses, pp 343–436 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor 1997).
  9. Boeke JD, Garfinkel DJ, Styles CA, Fink GR: Ty elements transpose through an RNA intermediate. Cell 40:491–500 (1985).
  10. Bolton EC, Mildvan AS, Boeke JD: Inhibition of reverse transcription in vivo by elevated manganese ion concentration. Mol Cell 9:879–889 (2002).
  11. Boutabout M, Wilhelm M, Wilhelm FX: DNA synthesis fidelity by the reverse transcriptase of the yeast retrotransposon Ty1. Nucleic Acids Res 29:2217–2222 (2001).
  12. Braiterman LT, Boeke JD: In vitro integration of retrotransposon Ty1: a direct physical assay. Mol Cell Biol 14:5719–5730 (1994a).
  13. Braiterman LT, Boeke JD: Ty1 in vitro integration: effects of mutations in cis and in trans. Mol Cell Biol 14:5731–5740 (1994b).
  14. Burns NR, Sailbil HR, White NS, Pardon JF, Timmins PA, Richardson SMH, Richards BM, Kingsman SM, Kingsman AJ: Symmetry, flexibility and permeability in the structure of yeast retrotransposon virus-like particles. EMBO J 11:1155–1164 (1992).
  15. Champoux JJ: Roles of ribonuclease H in reverse transcription, in Skalka AM, Goff SP (eds): Reverse Transcriptase, pp 103–118 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor 1993).
  16. Chapman KB, Bystrom AS, Boeke JD: Initiator methionine tRNA is essential for Ty1 transposition in yeast. Proc Natl Acad Sci USA 89:3236–3240 (1992).
  17. Charneau P, Clavel F: A single-stranded gap in human immunodeficiency virus unintegrated linear DNA defined by a central copy of the polypurine tract. J Virol 65:2415–2421 (1991).
  18. Charneau P, Alizon M, Clavel F: A second origin of DNA plus-strand synthesis is required for optimal immunodeficiency virus replication. J Virol 66:2814–2820 (1992).
  19. Charneau P, Mirambeau G, Roux P, Paulous S, Buc H, Clavel F: HIV-1 reverse transcription: a termination step at the center of the genome. J Mol Biol 241:651–662 (1994).
  20. Clare JJ, Belcourt M, Farabaugh PJ: Efficient translational frameshifting occurs within a conserved sequence of the overlap between the two genes of a yeast Ty1 transposon. Proc Natl Acad Sci USA 85:6816-6820 (1988).
  21. Cristofari G, Gabus C, Ficheux DD, Bona M, Le Grice SF, Darlix JL: Characterization of active reverse transcriptase and nucleoprotein complexes of the yeast retrotransposon Ty3 in vitro. J Biol Chem 274:36643–36648 (1999).
  22. Cristofari G, Ficheux D, Darlix JL: 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 (2000).
  23. Cristofari G, Bampi C, Wilhelm M, Wilhelm FX, Darlix JL: A 5′-3′ long-range interaction in Ty1 RNA controls its reverse transcription and retrotransposition. EMBO J 21:4368–4379 (2002).
  24. Darlix JL, Gabus C, Nugeyre MT, Clavel F, Barre-Sinoussi F: Cis elements and trans-acting factors involved in the RNA dimerization of the human immunodeficiency virus HIV-1. J Mol Biol 216:689–699 (1990).
  25. Darlix JL, Lapadat-Tapolski M, de Rocquigny H, Roques BP: First glimpses at structure-function relationships of the nucleocapsid protein of retroviruses. J Mol Biol 254:523–537 (1995).
  26. Dawson A, Hartswood E, Paterson T, Finnegan DJ: A LINE-like transposable element in Drosophila, the I factor, encodes a protein with properties similar to those of retroviral nucleocapsids. EMBO J 16:4448–4455 (1997).
  27. DeStefano JJ, Mallaber LM, Fay PJ, Bambara RA: Quantitative analysis of RNA cleavage during RNA-directed DNA synthesis by human immunodeficiency and avian myeloblastosis virus reverse transcriptases. Nucleic Acids Res 22:3793–3800 (1994).
  28. Devine SE, Boeke JD: Efficient integration of artificial transposons into plasmid targets in vitro: a useful tool for DNA mapping, sequencing and genetic analysis. Nucleic Acids Res 22:3765–3772 (1994).
  29. Drake JW: Rates of spontaneous mutation among RNA viruses. Proc Natl Acad Sci USA 90:4171–4175 (1993).
  30. Drake JW, Charlesworth B, Charlesworth D, Crow JF: Rates of spontaneous mutation. Genetics 148:1667–1686 (1998).
  31. Dvorin JD, Bell P, Maul GG, Yamashita M, Emerman M, Malim MH: Reassessment of the roles of integrase and the central DNA flap in human immunodeficiency virus type 1 nuclear import. J Virol 76:12087–12096 (2002).
  32. Eichinger DJ, Boeke JD: The DNA intermediate in yeast Ty1 element transposition copurifies with virus-like particles: cell-free Ty1 transposition. Cell 54:955–966 (1988).
  33. Eichinger DJ, Boeke JD: A specific terminal structure is required for Ty1 transposition. Genes Dev 4:324–330 (1990).
  34. Engelman A, Englund G, Orenstein JM, Martin MA, Craigie R: Multiple effects of mutations in human immunodeficiency virus type 1 integrase on viral replication. J Virol 69:2729–2736 (1995).
  35. Feng YX, Campbell S, Harvin D, Ehresmann B, Ehresmann C, Rein A: The human immunodeficiency virus type 1 Gag polyprotein has nucleic acid chaperone activity: possible role in dimerization of genomic RNA and placement of tRNA on the primer binding site. J Virol 73 :4251–4256 (1999).
  36. Feng YX, Moore SP, Garfinkel DJ, Rein A: The genomic RNA in Ty1 virus-like particles is dimeric. J Virol 74:10819–10821 (2000).
  37. Friant S, Heyman T, Wilhelm ML, Wilhelm FX: Extended interactions between the primer tRNAiMet and genomic RNA of the yeast Ty1 retrotransposon. Nucleic Acids Res 24:441–449 (1996).
  38. Friant S, Heyman T, Poch O, Wilhelm M, Wilhelm FX: Sequence comparison of the Ty1 and Ty2 elements of the yeast genome supports the structural model of the tRNAiMet-Ty1 RNA reverse transcription initiation complex. Yeast 13:639–645 (1997).
  39. Friant S, Heyman T, Bystrom AS, Wilhelm M, Wilhelm FX: Interactions between Ty1 retrotransposon RNA and the T and D regions of the tRNAiMet primer are required for initiation of reverse transcription in vivo. Mol Cell Biol 18:799–806 (1998).
  40. Furfine ES, Reardon JE: Reverse transcriptase-RNase H from the human immunodeficiency virus. J Biol Chem 266:406–412 (1991).
  41. Gabriel A, Boeke JD: Retrotransposon reverse transcription, in Skalka AM, Goff SP (eds) : Reverse Transcriptase, pp 275–328 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor 1993).
  42. Gabriel A, Willems M, Mules EH, Boeke JD: Replication infidelity during a single cycle of Ty1 retrotransposition. Proc Natl Acad Sci USA 93:7767–7771 (1996).
  43. Gabus C, Ficheux D, Rau M, Keith G, Sandmeyer S, Darlix JL: The yeast Ty3 retrotransposon contains a 5′-3′ bipartite primer-binding site and encodes nucleocapsid protein NCp9 functionally homologous to HIV-1 NCp7. EMBO J 17:4873–4880 (1998).
  44. Garfinkel DJ, Boeke JD, Fink GR: Ty element transposition: reverse transcriptase and virus-like particles. Cell 42:507–517 (1985).
  45. Garfinkel DJ, Hedge AM, Youngren SD, Copeland TD: Proteolytic processing of pol-TYB proteins from the yeast retrotransposon Ty1. J Virol 65:4573–4581 (1991).
  46. Gopalakrishnan V, Peliska JA, Benkovic SJ: Human immunodeficiency virus type 1 reverse transcriptase: spatial and temporal relationship between the polymerase and RNase H activities. Proc Natl Acad Sci USA 89:10763–10767 (1992).
  47. Götte M, Fackler S, Hermann T, Perola E., Cellai L, Gross HJ, Le Grice SF, Heumann H: HIV-1 reverse transcriptase-associated RNase H cleaves RNA/RNA in arrested complexes: implications for the mechanism by which RNase H discriminates between RNA/RNA and RNA/DNA. EMBO J 14:833–841 (1995).
  48. Götte M, Maier G, Onori AM, Cellai L, Wainberg MA, Heumann H: Temporal coordination between initiation of HIV (+)-strand DNA synthesis and primer removal. J Biol Chem 274:11159–11169 (1999).
  49. Grandgenett D, Quinn T, Hippenmeyer PJ, Oroszlan S: Structural characterization of the avian retrovirus reverse transcriptase and endonuclease domains. J Biol Chem 260:8243–8249 (1985).
  50. Hansen LJ, Sandmeyer SB: Characterization of a transcriptionally active Ty3 element and identification of the Ty3 integrase protein. J Virol 64:2599–2607 (1990).
  51. Heyman T, Agoutin B, Friant S, Wilhelm FX, Wilhelm ML: Plus-strand DNA synthesis of the yeast retrotransposon Ty1 is initiated at two sites, PPT1 next to the 3′ LTR and PPT2 within the pol gene. PPT1 is sufficient for Ty1 transposition. J Mol Biol 253:291–303 (1995).
  52. Heyman T, Wilhelm M, Wilhelm FX: The central PPT of the yeast retrotransposon Ty1 is not essential for transposition. J Mol Biol 331:315–320 (2003).
  53. Hu SC, Court DL, Zweig M, Levin JG: Murine leukemia virus pol gene products: analysis with antisera generated against reverse transcriptase and endonuclease fusion proteins expressed in Escherichia coli. J Virol 60:267–274 (1986).
  54. Huang H, Chopra R, Verdine GL, Harrison SC: Structure of covalently trapped catalytic complex of HIV-1 reverse transcriptase: implications for drug resistance. Science 282:1669–1675 (1998).
  55. Hungnes O, Tjotta E, Grinde B: The plus strand is discontinuous in a subpopulation of unintegrated HIV-1 DNA. Arch Virol 116:133–141 (1991).
  56. Hungnes O, Tjotta E, Grinde B: Mutations in the central polypurine tract of HIV-1 result in delayed replication. Virology 190:440–442 (1992).
  57. Ilyinskii PO, Desrosiers RC: Identification of a sequence element immediately upstream of the polypurine tract is essential for replication of simian immunodeficiency virus. EMBO J 17:3766–3774 (1998).
  58. Ishikawa T, Okui N, Kobayashi N, Sakuma R, Kitamura T, Kitamura Y: Monoclonal antibodies against the minimal DNA-binding domain in the carboxyl-terminal region of human immunodeficiency virus type 1 integrase. J Virol 73:4475–4480 (1999).
  59. Jacobo-Molina A, Ding J, Nanni RG, Clark AD, Lu X, Tantillo C, Williams RL, Kamer G, Ferris AL, Clark P: Crystal structure of human immunodeficiency virus type 1 reverse transcriptase complexed with double-stranded DNA at 3.0 Å resolution shows bent DNA. Proc Natl Acad Sci USA 90:6320–6324 (1993).
  60. Javanbakht H, Halwani R, Cen S, Saadatmand J, Musier-Forsyth K, Gottlinger H, Kleiman L: The interaction between HIV-1 Gag and human lysyl-tRNA synthetase during viral assembly. J Biol Chem 278:27644–27651 (2003).
  61. Kati WM, Johnson KA, Jerva LF, Anderson KS: Mechanism and fidelity of HIV reverse transcriptase. J Biol Chem 267:25988–25997 (1992).
  62. Katz RA, Skalka AM: The retroviral enzymes. Annu Rev Biochem 63:133–173 (1994).
  63. Kawakami K, Pande S, Faiola B, Moore DP, Boeke JD, Farabaugh PJ, Strathern JN, Nakamura Y, Garfinkel DJ: A rare tRNA Arg CUU that regulates Ty1 element ribosomal frameshifting is essential for Ty1 retrotransposition in S. cerevisiae. Genetics 135:309–320 (1993).
  64. Keeney JB, Chapman KB, Lauermann V, Voytas DF, Aström SU, von Pawel-Rammingen U, Byström A, Boeke JD: Multiple molecular determinants for retrotransposition in a primer tRNA. Mol Cell Biol 15:217–226 (1995).
  65. Kenna MA, Brachmann CB, Devine SE, Boeke JD: Invading the yeast nucleus: a nuclear localization signal at the C terminus of Ty1 integrase is required for transposition in vivo. Mol Cell Biol 18:1115–1124 (1998).
  66. Kim JM, Vanguri S, Boeke JD, Gabriel A, Voytas DF: Transposable elements and genome organization: a comprehensive survey of retrotransposons revealed by the complete Saccharomyces cerevisiae genome sequence. Genome Res 8:464–478 (1998).
  67. Kirchner J, Sandmeyer S: Proteolytic processing of Ty3 proteins is required for transposition. J Virol 67:19–28 (1993).
  68. Kirchner J, Sandmeyer SB: Ty3 integrase mutants defective in reverse transcription or 3′-end processing of extrachromosomal Ty3 DNA. J Virol 70:4737–4747 (1996).
  69. Kohlstaedt LA, Wang J, Friedman JM, Rice PA, Steitz TA: Crystal structure at 3.5Å resolution of HIV-1 reverse transcriptase complexed with an inhibitor. Science 256:1783–1790 (1992).
  70. Larder BA, Purifoy DJ, Powell KL, Darby G: Site-specific mutagenesis of AIDS virus reverse transcriptase. Nature 327:716–717 (1987).
  71. Larder BA, Kemp SD, Purifoy DJ: Infectious potential of human immunodeficiency virus type 1 reverse transcriptase mutants with altered inhibitor sensitivity. Proc Natl Acad Sci USA 86:4803–4807 (1989).
  72. Lauermann V, Boeke JD: The primer tRNA sequence is not inherited during Ty1 retrotransposition. Proc Natl Acad Sci USA 91:9847–9851 (1994).
  73. Lauermann V, Boeke JD: Plus strand strong-stop DNA transfer in yeast Ty retrotransposons. EMBO J 16:6603–6612 (1997).
  74. Lauermann V, Nam K, Trambley J, Boeke JD: Plus-strand strong-stop DNA synthesis in retrotransposon Ty1. J Virol 69:7845–7850 (1995).
  75. Lawler JF, Merkulov GV, Boeke JD: Frameshift signal transplantation and the unambiguous analysis of mutations in the yeast retrotransposon Ty1 Gag-Pol overlap region. J Virol 75:6769–6775 (2001).
  76. Lawler JF, Haeusser DP, Dull A, Boeke JD, Keeney JB: Ty1 defect in proteolysis at high temperature. J Virol 76:4233–4240 (2002a).
  77. Lawler JF, Merkulov GV, Boeke JD: A nucleocapsid functionality contained within the amino terminus of the Ty1 protease that is distinct and separable from proteolytic activity. J Virol 76:346–354 (2002b).
  78. Le Grice SF, Naas T, Wohlgensinger B, Schatz O: Subunit-selective mutagenesis indicates minimal polymerase activity in heterodimer-associated p51 HIV-1 reverse transcriptase. EMBO J 10:3905–3911 (1991).
  79. Limon A, Nakajima N, Lu R, Ghory HZ, Engelman A: Wild-type levels of nuclear localization and human immunodeficiency virus type 1 replication in the absence of the central DNA flap. J Virol 76:12078–12086 (2002).
  80. Litvak S, Sarih-Cottin L, Fournier M, Andreola M, Tarrago-Litvak L: Priming of HIV replication by tRNALys3: role of reverse transcriptase. Trends Biochem Sci 19:114–118 (1994).
  81. Luschnig C, Bachmair A: RNA packaging of yeast retrotransposon Ty1 in the heterologous host, Escherichia coli. Biol Chem 378:39–46 (1997).
  82. Mak J, Kleiman L: Primer tRNAs for reverse transcription. J Virol 71:8087–8095 (1997).
  83. Mak J, Jiang M, Wainberg MA, Hammarskjold ML, Rekosh D, Kleiman L: Role of Pr160gag-pol in mediating the selective incorporation of tRNALys into human immunodeficiency virus type 1 particles. J Virol 68:2065–2072 (1994).
  84. Malik HS, Eickbush TH: Phylogenetic analysis of ribonuclease H domains suggests a late, chimeric origin of LTR retrotransposable elements and retroviruses. Genome Res 11:1187–1197 (2001).
  85. Marquet R, Isel C, Ehresmann C, Ehresmann B: tRNAs as primer of reverse transcriptases. Biochimie 77:113–124 (1995).
  86. Martin-Rendon E, Hurd DW, Marfany G, Kingsman SM, Kingsman AJ: Identification of proteolytic cleavage sites within the gag-analogue protein of Ty1 virus-like particles. Mol Microbiol 22:1035–1043 (1996).
  87. McClure MA: Evolutionary history of reverse transcriptase in transcription, in Skalka AM, Goff SP (eds): Reverse Transcriptase, pp 425–444 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY 1993).
  88. Mellor J, Fulton AM, Dobson MJ, Roberts NA, Wilson W, Kingsman AJ, Kingsman SM: The Ty transposon of Saccharomyces cerevisiae determines the synthesis of at least three proteins. Nucleic Acids Res 13:6249–6263 (1985a).
  89. Mellor J, Malim MF, Gull K, Tuite MF, McCready S, Dibbayawan T, Kingsman SM, Kingsman AJ: Reverse transcriptase activity and Ty RNA are associated with virus-like particles in yeast. Nature 318:583–586 (1985b).
  90. Merkulov GV, Swiderek KM, Brachmann CB, Boeke JD: A critical proteolytic cleavage site near the C terminus of the yeast retrotransposon Ty1 Gag protein. J Virol 70:5548–5556 (1996).
  91. Merkulov GV, Lawler JF, Eby Y, Boeke JD: Ty1 proteolytic cleavage sites are required for transposition: all sites are not created equal. J Virol 75:638–644 (2001).
  92. Moore SP, Garfinkel DJ: Expression and partial purification of enzymatically active recombinant Ty1 integrase in Saccharomyces cerevisiae. Proc Natl Acad Sci USA 91:1843–1847 (1994).
  93. Moore SP, Garfinkel DJ: Correct integration of model substrates by Ty1 integrase. J Virol 74:11522–11530 (2000).
  94. Moore SP, Powers M, Garfinkel DJ: Substrate specificity of Ty1 integrase. J Virol 69:4683–4692 (1995).
  95. Moore SP, Rinckel LA, Garfinkel DJ: A Ty1 integrase nuclear localization signal required for retrotransposition. Mol Cell Biol 18:1105–1114 (1998).
  96. Mules EH, Uzun O, Gabriel A: In vivo Ty1 reverse transcription can generate replication intermediates with untidy ends. J Virol 72:6490–6503 (1998a).
  97. Mules EH, Uzun O, Gabriel A: Replication errors during in vivo Ty1 transposition are linked to heterogeneous RNase H cleavage sites. Mol Cell Biol 18:1094–1104 (1998b).
  98. Muller F, Bruhl KH, Freidel K, Kowallik KV, Ciriacy M: Processing of TY1 proteins and formation of Ty1 virus-like particles in Saccharomyces cerevisiae. Mol Gen Genet 207:421–429 (1987).
  99. Noad RJ, Al-Kaff NS, Turner DS, Covey SN: Analysis of polypurine tract-associated DNA plus-strand priming in vivo utilizing a plant pararetroviral vector carrying redundant ectopic priming elements. J Biol Chem 273:32568–32575 (1998).
  100. Nymark-McMahon MH, Sandmeyer SB: Mutations in nonconserved domains of Ty3 integrase affect multiple stages of the Ty3 life cycle. J Virol 73:453–465 (1999).
  101. Nymark-McMahon MH, Beliakova-Bethell NS, Darlix JL, Le Grice SF, Sandmeyer SB: Ty3 integrase is required for initiation of reverse transcription. J Virol 76:2804–2816 (2002).
  102. Oz I, Avidan O, Hizi A: Inhibition of the integrases of human immunodeficiency viruses type 1 and type 2 by reverse transcriptases. Biochem J 361:557–566 (2002).
  103. Padow M, Lai L, Deivanayagam C, DeLucas LJ, Weiss RB, Dunn DM, Wu X, Kappes JC: Replication of chimeric human immunodeficiency virus type 1 (HIV-1) containing HIV-2 integrase (IN): naturally selected mutations in IN augment DNA synthesis. J Virol 77:11050–11059 (2003).
  104. Peliska JA, Benkovic SJ: Mechanism of DNA strand transfer reactions catalyzed by HIV-1 reverse transcriptase. Science 258:1112–1118 (1992).
  105. Poch O, Sauvaget I, Delarue M, Tordo N: Identification of four conserved motifs among the RNA-dependent polymerase encoding elements. EMBO J 8:3867–3874 (1989).
  106. Pochart P, Agoutin B, Fix C, Keith G, Heyman T: A very poorly expressed tRNASer is highly concentrated together with replication primer initiator tRNAMet in the yeast Ty1 virus-like particles. Nucleic Acids Res 21:1517–1521 (1993a).
  107. Pochart P, Agoutin B, Rousset S, Chanet R, Doroszkiewicz V, Heyman T: Biochemical and electron microscope analyses of the DNA reverse transcripts present in the virus-like particles of the yeast transposon Ty1. Identification of a second origin of Ty1 DNA plus-strand synthesis. Nucleic Acids Res 21:3513–3520 (1993b).
  108. Prats AC, Sarih L, Gabus C, Litvak S, Keith G, Darlix JL: Small finger protein of avian and murine retroviruses has nucleic acid annealing activity and positions the replication primer tRNA onto genomic RNA. EMBO J 7:1777–1783 (1988).
  109. Rausch JW, Grice MK, Henrietta M, Nymark M, Miller JT, Le Grice SF: Interaction of p55 reverse transcriptase from the Saccharomyces cerevisiae retrotransposon Ty3 with conformationally distinct nucleic acid duplexes. J Biol Chem 275:13879–13887 (2000).
  110. Rein A, Henderson LE, Levin JG: Nucleic-acid-chaperone activity of retroviral nucleocapsid proteins: significance for viral replication. Trends Biochem Sci 23:297–301 (1998).
  111. Robson ND, Telesnitsky A: Effects of 3′ untranslated region mutations on plus-strand priming during Moloney murine leukemia virus replication. J Virol 73:948–957 (1999).
  112. Robson ND, Telesnitsky A: Selection of optimal polypurine tract region sequences during Moloney murine leukemia virus replication. J Virol 74:10293–10303 (2000).
  113. Rong L, Liang C, Hsu M, Kleiman L, Petitjean P, de Rocquigny H, Roques BP, Wainberg MA: Roles of the human immunodeficiency virus type 1 nucleocapsid protein in annealing and initiation versus elongation in reverse transcription of viral negative-strand strong-stop DNA. J Virol 72:9353–9358 (1998).
  114. Roth JF: The yeast Ty virus-like particles. Yeast 16:785–795 (2000).
  115. Schultz SJ, Zhang M, Kelleher CD, Champoux JJ: Polypurine tract primer generation and utilization by Moloney murine leukemia virus reverse transcriptase. J Biol Chem 274:34547–34555 (1999).
  116. Schultz SJ, Zhang M, Kelleher CD, Champoux JJ: Analysis of plus-strand primer selection, removal, and reutilization by retroviral reverse transcriptases. J Biol Chem 275:32299–32309 (2000).
  117. Stetor SR, Rausch JW, Guo MJ, Burnham JP, Boone LR, Waring MJ, Le Grice SF: Characterization of (+) strand initiation and termination sequences located at the center of the equine infectious anemia virus genome. Biochemistry 38:3656–3667 (1999).
  118. Tasara T, Maga G, Hottiger MO, Hubscher U: HIV-1 reverse transcriptase and integrase enzymes physically interact and inhibit each other. FEBS Lett 507:39–44 (2001).
  119. Telesnitsky A, Goff SP: Reverse transcriptase and the generation of retroviral DNA, in Coffin JM, Hughes SH, Varmus HE (eds): Retroviruses, pp 121–160 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY 1997).
  120. Trentin B, Rebeyrotte N, Mamoun RZ: Human T-cell leukemia virus type 1 reverse transcriptase (RT) originates from the pro and pol open reading frames and requires the presence of RT-RNase H (RH) and RT-RH-Integrase proteins for its activity. J Virol 72:6504–6510 (1998).
  121. Tsurutani N, Kubo M, Maeda Y, Ohashi T, Yamamoto N, Kannagi M, Masuda T: Identification of critical amino acid residues in human immunodeficiency virus type 1 IN required for efficient proviral DNA formation at steps prior to integration in dividing and nondividing cells. J Virol 74:4795–4806 (2000).
  122. Uzun O, Gabriel A: A Ty1 reverse transcriptase active-site aspartate mutation blocks transposition but not polymerization. J Virol 75:6337–6347 (2001).
  123. Varmus H: Retroviruses. Science 240:1427–1435 (1988).
  124. Vartaninan JP, Sommer P, Wain-Hobson S: Death and the retrovirus. Trends Mol Med 9:409–413 (2003).
  125. Voytas DF, Boeke JD: Yeast retrotransposons and tRNAs. Trends Genet 9:421–427 (1993).
  126. Voytas DF, Boeke JD: Ty1 and Ty5 of Saccharomyces cerevisiae, in Craig NL, Craigie R, Lambowitz A: Mobile DNA II, pp 631–656 (ASM Press, Washington DC 2002).
  127. Werner S, Wohrl BM: Asymmetric subunit organization of heterodimeric Rous sarcoma virus reverse transcriptase alphabeta: localization of the polymerase and RNase H active sites in the alpha subunit. J Virol 74:3245–3252 (2000).
  128. Whitwam T, Peretz M, Poeschla E: Identification of a central DNA flap in feline immunodeficiency virus. J Virol 75:9407–9414 (2001).
  129. Wilhelm M, Wilhelm FX, Keith G, Agoutin B, Heyman T: Yeast Ty1 retrotransposon: the minus-strand primer binding site and a cis-acting domain of the Ty1 RNA are both important for packaging of primer tRNA inside virus-like particles. Nucleic Acids Res 22:4560–4565 (1994).
  130. Wilhelm M, Heyman T, Boutabout M, Wilhelm FX: A sequence immediately upstream of the plus-strand primer is essential for plus-strand DNA synthesis of the Saccharomyces cerevisiae Ty1 retrotransposon. Nucleic Acids Res 27:4547–4552 (1999).
  131. Wilhelm M, Boutabout M, Wilhelm FX: Expression of an active form of recombinant Ty1 reverse transcriptase in Escherichia coli: a fusion protein containing the C-terminal region of the Ty1 integrase linked to the reverse transcriptase-RNase H domain exhibits polymerase and RNase H activities. Biochem J 348:337–342 (2000).
  132. Wilhelm M, Uzun O, Mules EH, Gabriel A, Wilhelm FX: Polypurine tract formation by Ty1 RNase H. J Biol Chem 276:47695–47701 (2001).
  133. Wilhelm FX, Wilhelm M, Gabriel A: Extension and cleavage of the polypurine tract plus-strand primer by Ty1 reverse transcriptase. J Biol Chem 278:47678–47684 (2003).
  134. Wilson W, Malim HM, Mellor J, Kingsman AJ, Kingsman SM: Expression strategies of the yeast retrotransposon Ty: a short sequence directs ribosomal frameshifting. Nucleic Acids Res 14:7001–7017 (1986).
  135. Wisniewski M, Balakrishnan M, Palaniappan C, Fay PJ, Bambara RA: The sequential mechanism of HIV reverse transcriptase RNase H. J Biol Chem 275:37664–37671 (2000a).
  136. Wisniewski M, Balakrishnan M, Palaniappan C, Fay PJ, Bambara RA: Unique progressive cleavage mechanism of HIV reverse transcriptase RNase H. Proc Natl Acad Sci USA 97:11978–11983 (2000b).
  137. Wisniewski M, Chen Y, Balakrishnan M, Palaniappan C, Roques BP, Fay PJ, Bambara RA: Substrate requirements for secondary cleavage by HIV-1 reverse transcriptase RNase H. J Biol Chem 277:28400–28410 (2002).
  138. Wöhrl BM, Moelling K: Interaction of HIV-1 ribonuclease H with polypurine tract containing RNA-DNA hybrids. Biochemistry 29:10141–10147 (1990).
  139. Wu X, Liu H, Xiao H, Conway JA, Hehl E, Kalpana GV, Prasad V, Kappes JC: Human immunodeficiency virus type 1 integrase protein promotes reverse transcription through specific interactions with the nucleoprotein reverse transcription complex. J Virol 73:2126–2135 (1999).
  140. Xiong Y, Eickbush TH: Origin and evolution of retroelements based upon their reverse transcriptase sequences. EMBO J 9:3353–3362 (1990).
  141. Xu H, Boeke JD: High-frequency deletion between homologous sequences during retrotransposition of Ty elements in Saccharomyces cerevisiae. Proc Natl Acad Sci USA 84:8553–8557 (1987).
  142. Xu H, Boeke JD : Host genes that influence transposition in yeast: the abundance of a rare tRNA regulates Ty1 transposition frequency. Proc Natl Acad Sci USA 87:8360–8364 (1990a).
  143. Xu H, Boeke JD: Localization of sequences required in cis for yeast Ty1 element transposition near the long terminal repeats: analysis of mini-Ty1 elements. Mol Cell Biol 10:2695–2702 (1990b).
  144. Youngren SD, Boeke JD, Sanders NJ, Garfinkel DJ: Functional organization of the retrotransposon Ty from Saccharomyces cerevisiae: Ty protease is required for transposition. Mol Cell Biol 8:1421–1431 (1988).
  145. Yu Q, Morrow CD: Essential regions of the tRNA primer required for HIV-1 infectivity. Nucleic Acids Res 28:4783–4789 (2000).
  146. Yung E, Sorin M, Pal A, Craig E, Morozov A, Delattre O, Kappes J, Ott D, Kalpana GV: Inhibition of HIV-1 virion production by a transdominant mutant of integrase interactor 1. Nat Med 7:920–926 (2001).
  147. Zennou V, Petit C, Guetard D, Nerhbass U, Montagnier L, Charneau P: HIV-1 genome nuclear import is mediated by a central DNA flap. Cell 101:173–185 (2000).


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