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Gene silencing as an adaptive defence against viruses

Abstract

Gene silencing was perceived initially as an unpredictable and inconvenient side effect of introducing transgenes into plants. It now seems that it is the consequence of accidentally triggering the plant's adaptive defence mechanism against viruses and transposable elements. This recently discovered mechanism, although mechanistically different, has a number of parallels with the immune system of mammals.

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Figure 1: Potato plants challenged with potato virus Y.
Figure 2: Proposed mechanism, based on RNAi, for dsRNA-directed ssRNA cleavage in PTGS.
Figure 3: Distribution of domains on DCR1-like and AGO1-like proteins.
Figure 4: A model for the initiation and operation of PTGS.
Figure 5: Possible ways in which transposons may generate hpRNA or dsRNA.
Figure 6: Tobacco plants showing potato virus Y (PVY) susceptibility, immunity and resistant/recovery symptoms.
Figure 7: A model for mobile PTGS and methylation signals.

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References

  1. Mayo, M. A. Developments in plant virus taxonomy since the publication of the 6th ICTV report. Arch. Virol. 144, 1659–1666 (1999).

    CAS  PubMed  Google Scholar 

  2. Bennetzen, J. L. Transposable element contributions to plant gene and genome evolution. Plant Mol. Biol. 42, 251–269 (2000).

    CAS  PubMed  Google Scholar 

  3. Kumar, A. & Bennetzen, J. L. Plant retrotransposons. Annu. Rev. Genet. 33, 479–452 (1999).

    CAS  PubMed  Google Scholar 

  4. Martienssen, R. Transposons, DNA methylation and gene control. Trends Genet. 14, 263–264 (1998).

    CAS  PubMed  Google Scholar 

  5. Rothstein, S. J., Dimaio, J., Strand, M. & Rice, D. Stable and inheritable inhibition of the expression of nopaline synthase in tobacco expressing antisense RNA. Proc. Natl Acad. Sci. USA 84, 8439–8443 (1987).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  6. Simons, R. W. & Kleckner, N. Translational control of IS10 transposition. Cell 34, 683–691 (1983).

    CAS  PubMed  Google Scholar 

  7. Hamilton, A. J., Lycett, G. W. & Grierson, D. Antisense gene that inhibits synthesis of the hormone ethylene in transgenic plants. Nature 346, 284–287 (1990).

    ADS  CAS  Google Scholar 

  8. Napoli, C., Lemieux, C. & Jorgensen, R. Introduction of a chimeric chalcone synthase gene into petunia results in reversible co-suppression of homologous genes in trans. Plant Cell 7, 599–609 (1990).

    Google Scholar 

  9. Van der Krol, A. R., Mur, L. A., Beld, K., Mol, J. N. M. & Stuitje, A. R. Flavonoid genes in petunia: addition of a limited number of gene copies may lead to suppression of gene expression. Plant Cell 2, 291–299 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. De Carvalho, F. et al. Suppression of the β-1,3 glucanase transgene expression in homozygous plants. EMBO J. 11, 2595–2602 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Powell-Abel, P. et al. Delay of disease development in transgenic plants that express the tobacco mosaic virus coat protein gene. Science 232, 738–743 (1986).

    ADS  Google Scholar 

  12. Lindbo, J. A. & Dougherty, W. G. Untranslatable transcripts of the tobacco etch virus coat protein gene sequence can interfere with tobacco etch virus replication in transgenic plants and protoplasts. Virology 189, 725–733 (1992).

    CAS  PubMed  Google Scholar 

  13. Dougherty, W. G. & Parks, T. D. Transgenes and gene suppression: telling us something new? Curr. Opin. Cell Biol. 7, 399–405 (1995).

    CAS  PubMed  Google Scholar 

  14. English, J. J., Mueller, E. & Baulcombe, D. C. Suppression of virus accumulation in transgenic plants exhibiting silencing of nuclear genes. Plant Cell 8, 787–797 (1996).

    Google Scholar 

  15. Tanzer, M. M., Thompson, W. F., Law, M. D., Wernsman, E. A. & Ukenes, S. Characterization of post-transcriptionally suppressed transgene expression that confers resistance to tobacco etch virus infection in tobacco. Plant Cell 9, 1411–1423 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Voinnet, O., Vain, P., Angell, S. & Baulcombe, D. C. Systemic spread of sequence-specific transgene RNA degradation in plants is initiated by localized introduction of ectopic promoterless DNA. Cell 95, 177–187 (1998).

    CAS  PubMed  Google Scholar 

  17. Wassenegger, M. & Pelissier, T. A model for RNA-mediated gene silencing in higher plants. Plant Mol. Biol. 37, 349–362 (1998).

    CAS  PubMed  Google Scholar 

  18. Waterhouse, P. M., Graham, M. W. & Wang, M.-B. Virus resistance and gene silencing in plants can be induced by simultaneous expression of sense and antisense RNA. Proc. Natl Acad. Sci USA 95, 13959–13964 (1998).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  19. Wang, M.-B. & Waterhouse, P. M. High efficiency silencing of a β-glucuronidase gene in rice is correlated with repetitive transgene structure but is independent of DNA methylation. Plant Mol. Biol. 43, 67–82 (2000).

    CAS  PubMed  Google Scholar 

  20. Smith, N. A. et al. Total silencing by intron-spliced hairpin RNAs. Nature 407, 319–320 (2000).

    ADS  CAS  PubMed  Google Scholar 

  21. Stam, M. et al. Distinct features of post-transcriptional gene silencing by antisense transgenes in single copy and inverted T-DNA repeat loci. Plant J. 21, 27–42 (2000).

    CAS  PubMed  Google Scholar 

  22. Morris T. J. & Dodds, J. A. Isolation and analysis of double stranded RNA from virus-infected plant and fungal tissue. Phytopathology 69, 854–858 (1979).

    CAS  Google Scholar 

  23. Blumenthal, T. & Carmichael, G. G. RNA replication: function and structure of Qβ replicase. Annu. Rev. Biochem. 48, 525–548 (1979).

    CAS  PubMed  Google Scholar 

  24. Buck, K. W. Replication of tobacco mosaic virus RNA. Phil. Trans. R. Soc. Lond. B 354, 613–627 (1999).

    CAS  Google Scholar 

  25. Ogawa, T., Hori, T. & Ishida, I. Virus-induced death in plants expressing the mammalian 2′,5′ oligoadenylate system. Nature Biotechnol. 14, 1566–1569 (1996).

    CAS  Google Scholar 

  26. Baulcombe, D. C. Fast forward genetics based in virus-induced gene silencing. Curr. Opin. Plant Biol. 2, 109–113 (1999).

    CAS  PubMed  Google Scholar 

  27. Lee, K. Y., Baden, C., Howie, W. J., Bedbrook, J. & Dunsmuir, P. Post-transcriptional gene silencing of ACC synthase in tomato results from cytoplasmic RNA degradation. Plant J. 12, 1127–1137 (1997).

    CAS  Google Scholar 

  28. Metzlaff, M., O'Dell, M., Cluster, P. D. & Flavell, R. B. RNA-mediated RNA degradation and chalcone synthase A silencing in Petunia . Cell 88, 845–854 (1997).

    CAS  PubMed  Google Scholar 

  29. Hamilton, A. J. & Baulcombe, D. C. A species of small antisense RNA in posttranscriptional gene silencing in plants. Science 286, 950–952 (1999).

    CAS  PubMed  Google Scholar 

  30. Mette, M. F., Aufatz, W., van der Winden, J., Matzke, M. A & Matzke, A. J. M. Transcriptional silencing and promoter methylation triggered by double stranded RNA. EMBO J. 19, 5194–5201 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Llave, C., Kasschau, K. D. & Carrington, J. C. Virus-encoded suppressor of posttranscriptional gene silencing targets a maintenance step in the silencing pathway. Proc. Natl Acad. Sci. USA 97, 13401–13406 (2000).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  32. Dalmay, T., Hamilton, A., Rudd, S., Angell, S. & Baulcombe, D. C. An RNA-dependent RNA polymerase gene in Arabidopsis is required for post-transcriptional gene silencing mediated by a transgene but not by a virus. Cell 101, 543–553 (2000).

    CAS  PubMed  Google Scholar 

  33. Hutvagner, G., Mlynarova, L. & Nap, J. P. Detailed characterization of the posttranscriptional gene-silencing-related small RNA in a GUS gene-silenced tobacco. RNA 6, 1445–1454 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Fire, A. et al. Potent and specific genetic interference by double stranded RNA in Caenorhabditis elegans . Nature 391, 806–811 (1998).

    ADS  CAS  PubMed  Google Scholar 

  35. Kennerdel, J. R. & Carthew, R. W. Use of dsRNA-mediated genetic interference to demonstrate that frizzled and frizzled 2 act in the wingless pathway. Cell 95, 1017–1026 (1998).

    Google Scholar 

  36. Zamore, P. D., Tuschl, T., Sharp, P. A. & Bartel, D. P. RNAi: double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell 101, 25–33 (2000).

    CAS  PubMed  Google Scholar 

  37. Yang, D., Lu, H. & Erickson, J. W. Evidence that processed small dsRNAs may mediate sequence-specific mRNA degradation during RNAi in Drosophila embryos. Curr. Biol. 10, 1191–1200 (2000).

    CAS  PubMed  Google Scholar 

  38. Hammond, S. C., Bernstein, E., Beach, D. & Hannon, G. J. An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature 404, 293–296 (2000).

    ADS  CAS  PubMed  Google Scholar 

  39. Bernstein, E., Caudy, A. A., Hammond, S. M. & Hannon, G. J. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 409, 363–366 (2001).

    ADS  CAS  PubMed  Google Scholar 

  40. Elbashir, S. M., Lendeckel, W. & Tuschl, T. RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes Dev. 15, 188–200 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Holtorf, H., Schob, H., Kunz, C., Waldvogel, R. & Meins, F. Stochastic and nonstochastic post-transcriptional silencing of chitinase and β-1,3-glucanase genes involves increased RNA turnover—possible role for ribosome-independent RNA degradation. Plant Cell 11, 471–483 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Zou, C., Zhang, Z., Wu, S. & Osterman, J. C. Molecular cloning and characterization of a rabbit eIF2C protein. Gene 211, 187–194 (1998).

    CAS  PubMed  Google Scholar 

  43. Cogoni, C. & Macino, G. Gene silencing in Neurospora crassa requires a protein homologous to RNA-dependent RNA polymerase. Nature 399, 166–169 (1999).

    ADS  CAS  PubMed  Google Scholar 

  44. Mourrain, P. et al. Arabidopsis SGS2 and SGS3 genes are required for posttranscriptional gene silencing and natural virus resistance. Cell 101, 533–542 (2000).

    CAS  PubMed  Google Scholar 

  45. Smardon, A. et al. EGO-1 is related to RNA-directed RNA polymerase and functions in germ-line development and RNA interference in C. elegans . Curr. Biol. 10, 169–178 (2000).

    CAS  PubMed  Google Scholar 

  46. Catalanotto, C., Azzalin, G., Macino, G. & Cogoni, C. Gene silencing in worms and fungi. Nature 404, 245 (2000).

    ADS  CAS  PubMed  Google Scholar 

  47. Tabara, H. et al. The rde-I gene, RNA interference, and transposon silencing in C. elegans . Cell 99, 123–132 (1999).

    CAS  PubMed  Google Scholar 

  48. Fagard, M., Boutet, S., Morel, J.-B., Bellini, C. & Vaucheret, H. AGO1, QDE-2, and RDE-1 are related proteins required for post-transcriptional gene silencing in plants, quelling in fungi and RNA interference in animals. Proc. Natl Acad. Sci. USA 97, 11650–11654 (2000).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  49. Ketting, R. F., Haverkamp, T. H. A., van Luenen, H. G. A. & Plasterk, R. H. A. mut-7 of C. elegans, required for transposon silencing and RNA interference, is a homolog of Werner Syndrome helicase and RNase D. Cell 99, 133–141 (1999).

    CAS  PubMed  Google Scholar 

  50. Domeier, M. E. et al. A link between RNA interference and nonsense-mediated decay in Caenorhabditis elegans . Science 289, 1928–1930 (2000).

    ADS  CAS  PubMed  Google Scholar 

  51. Cogoni, C. & Macino, G. Post-transcriptional gene silencing in Neurospora by a ReqQ DNA helicase. Science 286, 342–344 (1999).

    Google Scholar 

  52. Wu-Scarf, D., Jeong, B.-R., Zhang, C. & Cerutti, H. Transgene and transposon silencing in Chlamydomonas reinhardtii by a DEAH-box RNA helicase. Science 290, 1159–1162 (2000).

    ADS  Google Scholar 

  53. Dalmay, T., Horsefield, R., Braunstein, T. H. & Baulcombe, D. C. SDE3 encodes an RNA helicase required for post-transcriptional gene silencing in Arabidopsis . EMBO J. 20, 2069–2077 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Cerruti, L., Mian, N. & Bateman, A. Domains in gene silencing and cell differentiation proteins: the novel PAZ domain and redefinition of the Piwi domain. Trends Biochem. Sci. 25, 481–482 (2000).

    Google Scholar 

  55. Kooter, J. M., Matzke, M. A. & Meyer, P. Listening to the silent genes: transgene silencing, gene regulation and pathogen control. Trends. Plant Sci. 4, 340–347 (1999).

    CAS  PubMed  Google Scholar 

  56. Morel, J.-B., Mourrain, P., Berlin, C. & Vaucheret, H. DNA methylation and chromatin structure mutants affect both post-transcriptional and transcriptional transgene silencing in Arabidopsis . Curr. Biol. 10, 1591–1594 (2001).

    Google Scholar 

  57. Jones, A. L. et al. De novo methylation and co-suppression induced by a cytoplasmically replicating plant RNA virus. EMBO J. 17, 6385–6393 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Wang, M.-B., Wesley, S. V., Finnegan, E. J., Smith, N. A. & Waterhouse, P. M. Replicating satellite RNA induces sequence specific DNA methylation and truncated transcripts in plants. RNA 7, 16–28 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Van Houdt, H., Ingelbrecht, I., van Montagu, M. & Depicker, A. Post-transcriptional silencing of a neomycin phosphotransferase II transgene correlates with the accumulation of unproductive RNAs and with increased cytosine methylation of 3′ flanking regions. Plant J. 12, 379–392 (1997).

    CAS  Google Scholar 

  60. Yoder, J. A., Walsh, C. P. & Bestor, T. H. Cytosine methylation and ecology of intragenomic parasites. Trends Genet. 13, 335–340 (1997).

    CAS  PubMed  Google Scholar 

  61. Brutnell, T. P. & Dellaporta, S. L. Somatic inactivation and reactivation of Ac associated changes in cytosine methylation and transposase expression. Genetics 138, 213–225 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. San Miguel, P. et al. Nested transposons in the intergenic regions of the maize genome. Science 257, 765–768 (1996).

    ADS  Google Scholar 

  63. Bennetzen, J. L. The contributions of retroelements to plant genome organisation, function and evolution. Trends Microbiol. 4, 347–353 (1993).

    Google Scholar 

  64. Kunze, R., Saedler, H. & Lonnig, W. E. Plant transposable elements. Adv. Bot. Res. 27, 331–470 (1997).

    CAS  Google Scholar 

  65. Bennetzen, J. L. The Mutator transposable element system of maize. Curr. Top. Microbiol. Immunol. 204, 195–229 (1996).

    CAS  PubMed  Google Scholar 

  66. Schlappi, M., Raina, R. & Fedoroff, N. Epigenetic regulation of the maize Spm transposable element: novel activation of a methylated promoter by TnpA. Cell 77, 427–437 (1994).

    CAS  PubMed  Google Scholar 

  67. Liu, W. M., Maraia, R. J., Rubin, C. M. & Schmid, C. W. Alu transcripts: cytoplasmic localisation and regulation by DNA methylation. Nucleic Acids Res. 22, 1087–1095 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Singer, T., Yordan, C. & Martienssen, R. A. Robertson's Mutator transposons in A. thaliana are regulated by the chromatin-remodeling gene Decrease in DNA Methylation (DDM1). Genes Dev. 15, 591–602 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Miura, A. et al. Mobilization of transposons by a mutation abolishing full DNA methylation in Arabidopsis . Nature 411, 212–214 (2001).

    ADS  CAS  PubMed  Google Scholar 

  70. Hirochika, H., Okamoto, H. & Kakutani, T. Silencing of retrotransposons in arabidopsis and reactivation by the ddm1 mutation. Plant Cell 12, 357–368 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Hershberger, R. J. Characterization of the major transcripts encoded by the regulatory MuDR transposable element of maize. Genetics 140, 1087–1098 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Covey, S. N., Al-Kaff, N. S., Langara, A. & Turner, D. S. Plants combat infection by gene silencing. Nature 385, 781–782 (1997).

    ADS  CAS  Google Scholar 

  73. Palauqui, J. C., Elmayan, T., Pollien, J. M. & Vaucheret, H. Systemic acquired silencing: transgene specific post transcriptional silencing is transmitted by grafting from silenced stocks to non-silenced scions. EMBO J. 16, 4738–4745 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Lucas, W. J. & Gilbertson, R. L. Plasmodesmata in relation to viral movement within leaf tissues. Annu. Rev. Phytopathol. 32, 387–411 (1994).

    CAS  Google Scholar 

  75. Ding, B., Kwon, M. O., Hammond, R. & Owens, R. Cell to cell movement of potato spindle tuber viroid. Plant J. 12, 931–936 (1997).

    CAS  PubMed  Google Scholar 

  76. Lucas, W. J. et al. Selective trafficking of KNOTTED1 homoeodomain protein and its mRNA through plasmodesmata. Science 270, 1980–1983 (1995).

    ADS  CAS  PubMed  Google Scholar 

  77. Kuhn, C., Franceschi, V. R., Schulz, A., Lemoine, R. & Frommer, W. B. Macromolecular trafficking indicated by localisation and turnover of sucrose in enucleate sieve elements. Science 275, 1298–1300 (1997).

    CAS  PubMed  Google Scholar 

  78. Ruiz-Medrano, R., Xocosnostle-Cazares, B. & Lucas, W. J. Phloem long-distance transport of CmNACP mRNA: implications for supracellular regulation in plants. Development 126, 4405–4419 (1999).

    CAS  PubMed  Google Scholar 

  79. Sasaki, T., Chino, M., Hayashi, H. & Fujiwara, T. Detection of mRNA species in phloem sap. Plant Cell Physiol. 39, 895–897 (1998)

    CAS  PubMed  Google Scholar 

  80. Kasschau, K. D. & Carrington J. C. A counter-defensive strategy of plant viruses: suppression of post-transcriptional gene silencing. Cell 95, 461–470 (1998).

    CAS  PubMed  Google Scholar 

  81. Marathe, M. et al. Plant viral suppressors of post-transcriptional silencing do not suppress transcriptional silencing. Plant J. 22, 51–59 (2000).

    MathSciNet  CAS  PubMed  Google Scholar 

  82. Ratcliff, F., Harrison, B. D. & Baulcombe, D. C. A similarity between viral defense and gene silencing in plants. Science 276, 1558–1560 (1997).

    CAS  PubMed  Google Scholar 

  83. Ratcliff, F. G., MacFarlane, S. S. & Baulcombe, D. C. Gene silencing without DNA: RNA mediated cross protection between viruses. Plant Cell 11, 1207–1215 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Brigneti, G. et al. Viral pathogenicity determinants are suppressors of transgene silencing in Nicotiana bentamiana . EMBO J. 17, 6739–6746 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Li, H. W. et al. Strong host resistance targeted against a viral suppressor of the plant gene silencing defence mechanism. EMBO J. 18, 2683–2691 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Voinnet, O., Lederer, C. & Baulcombe, D. C. A viral movement protein prevents spread of the gene silencing signal in Nicotiana benthamiana . Cell 103, 157–167 (2000).

    CAS  PubMed  Google Scholar 

  87. Mallory, A. C. et al. HC-Pro suppression of gene silencing eliminates the small RNAs but not the transgene methylation or the mobile signal. Plant Cell 13, 571–583 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Jacobsen, S. E., Running, M. P. & Meyerowitz, E. M. Disruption of an RNA helicase/RNaseIII gene in Arabidopsis causes unregulated cell division in floral meristems. Development 126, 5231–5243 (1999).

    CAS  PubMed  Google Scholar 

  89. Anandakshmi, R. et al. A calmodulin-related protein that suppresses posttranscriptional gene silencing in plants. Science 290, 142–144 (2000).

    ADS  Google Scholar 

  90. Wang, M.-B., Abbott, D. & Waterhouse, P. M. A single copy of a virus-derived transgene encoding hairpin RNA gives immunity to barley yellow dwarf virus. Mol. Plant Pathol. 1, 347–356 (2000).

    CAS  PubMed  Google Scholar 

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Acknowledgements

We thank M.-A. Grandbastion, R. Hull and our colleagues at P.I. for being so generous with their time and knowledge. Thanks also to V. Vance for access to her manuscript before publication.

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Waterhouse, P., Wang, MB. & Lough, T. Gene silencing as an adaptive defence against viruses. Nature 411, 834–842 (2001). https://doi.org/10.1038/35081168

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