Trends in Genetics
Volume 17, Issue 8, 1 August 2001, Pages 449-459
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Review
RNA silencing as a plant immune system against viruses

https://doi.org/10.1016/S0168-9525(01)02367-8Get rights and content

Abstract

‘RNA silencing’ refers to related processes of post-trancriptional control of gene expression found in plants, animals and fungi. A unifying feature of RNA silencing is that it mediates sequence-specific degradation of target transcripts, recruiting RNA molecules of 21–23 nucleotides as specificity determinants. In higher plants, RNA silencing serves as an adaptive, antiviral defence system, which is transmitted systemically in response to localized virus challenge. Plant viruses have elaborated a variety of counter-defensive measures to overcome the host silencing response. One of these strategies is to produce proteins that target the cell autonomous or signalling steps of RNA silencing. It is not known whether a similar antiviral mechanism also operates in animal cells.

Section snippets

A generalized response to viruses

For decades, the prophylactic inoculation of attenuated viral strains has been used to control viral diseases in plants. The rationale for this form of vaccination, called ‘cross-protection’, came from classic observations that many infections in plants prevent the secondary accumulation of viral strains that are closely related to the primary-infecting virus 8. For several plant viruses, the mechanism underlying cross-protection is a post-transcriptional and RNA-mediated process that targets

Viral-encoded suppressors of RNA silencing

The simple observation that viruses infect plants at all highlights the fact that they have somehow evolved to avoid or suppress the host RNA silencing response. This idea was first prompted by the demonstration that co-inoculation of a normally innocuous virus with potyviruses leads to an extreme accentuation of symptoms caused by high accumulation of the non-potyviral partner. It was shown that this synergism results from suppression, by the Hc-protease (HcPro) of potyviruses, of a host

Initiation: a central role for double-stranded RNA

Transgene constructs engineered to produce dsRNA as opposed to single-stranded (ss) RNA cause a high incidence of RNA silencing in plants 28, 29, consistent with the demonstration that dsRNA is sufficient to trigger RNAi in animals 30. Studies in transgenic plants that constitutively express the single-stranded PVX RNA also indicate that replication (during which dsRNA intermediates are formed), rather than mere accumulation of the viral genome, is required for RNA silencing activation 31.

Targets and mode of action of silencing suppressors

At present, little is known about the targets of viral-encoded silencing suppressors. Their modes of action have been largely inferred from overexpression experiments in different transgene-induced silencing systems, an approach that might have some limitations (Box 2). In principle, viral-encoded suppressors could affect – directly or indirectly – any step of the model depicted in Fig. 2. One could argue, however, that factors targeted against silencing components that are essential to the

An antiviral mechanism in animals?

Although, in animals, it is clear that RNA silencing plays a role in genome defence against transposable elements, there is still no evidence for it having an antiviral function. However, tools are available to address this important question. A recombinant Sindbis RNA virus (SIN) has been modified as a vector for endogenous gene overexpression in insects 58. Engineering this virus with exon fragments, rather than full-length cDNA, could help to elucidate whether VIGS operates in host organisms

Conclusion

Significant advances have been made in our understanding of the role and mechanism of RNA silencing over recent years. There is now strong evidence that RNA silencing operates as an innate antiviral defence in higher plants. Consistent with this finding, many plant viruses have elaborated proteins that suppress various steps of RNA silencing, a necessary adaptation if they are to replicate and spread in a plant. Forward genetic screens in Arabidopsis have revealed distinct genetic requirements

Acknowledgements

I thank all my colleagues at the Sainsbury Laboratory for fruitful discussions. I am particularly grateful to D. Baulcombe, A. Hamilton, T. Dalmay and J. Peart for critical reading of the manuscript. I acknowledge financial support from the European Union (Training and mobility of Researchers category 20, grant no. ERB4001GT9740039). Work in the Sainsbury Laboratory is supported by the Gatsby Charitable Foundation.

References (71)

  • M. Fagard

    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. U. S. A.

    (2000)
  • P. Mourrain

    Arabidopsis SGS2 and SGS3 genes are required for posttranscriptional gene silencing and natural virus resistance

    Cell

    (2000)
  • T. Dalmay

    SDE3 encodes an RNA helicase required for post-transcriptional gene silencing in Arabidopsis

    EMBO J.

    (2001)
  • R. Anandalakshmi

    A calmodulin-related protein that suppresses posttranscriptional gene silencing in plants

    Science

    (2000)
  • A. Lucy

    Suppression of post-transcriptional gene silencing by a plant viral protein localized in the nucleus

    EMBO J.

    (2000)
  • P. Gonczy

    Functional genomic analysis of cell division in C. elegans using RNAi of genes on chromosome III

    Nature

    (2000)
  • R.A. Burton

    Virus-induced silencing of a plant cellulose synthase gene

    Plant Cell

    (2000)
  • A.R. van der Krol

    Flavonoid genes in petunia: addition of a limited number of gene copies may lead to a suppression of gene expression

    Plant Cell

    (1990)
  • T. Elmayan et al.

    Single copies of a 35S-driven transgene can undergo post-transcriptional silencing at each generation or can be transcriptionally inactivated in trans by a 35S silencer

    Plant J.

    (1996)
  • F. Wianny et al.

    Specific interference with gene function by double-stranded RNA in early mouse development

    Nat. Cell Biol.

    (2000)
  • S.M. Hammond

    Post-transcriptional gene silencing by double-stranded RNA

    Nat. Rev. Genet.

    (2001)
  • R. Ketting

    mut-7 of C. elegans, required for transposon silencing and RNA interference, is a homolog of Werner syndrome helicase and RnaseD

    Cell

    (1999)
  • R.E.F. Matthews

    Plant Virology

    (1991)
  • F. Ratcliff

    Gene silencing without DNA: RNA-mediated cross protection between viruses

    Plant Cell

    (1999)
  • J-C. Palauqui

    Systemic acquired silencing: transgene-specific post-transcriptional silencing is transmitted by grafting from silenced stocks to non-silenced scions

    EMBO J.

    (1997)
  • J-C. Palauqui et al.

    Transgenes are dispensable for the RNA degradation step of cosuppression

    Proc. Natl. Acad. Sci. U. S. A.

    (1998)
  • O. Voinnet et al.

    Systemic signalling in gene silencing

    Nature

    (1997)
  • O. Voinnet

    Systemic spread of sequence-specific transgene RNA degradation is initiated by localised introduction of ectopic promoterless DNA

    Cell

    (1998)
  • S. Sonoda et al.

    Graft transmission of post-transcriptional gene silencing: target specificity for RNA degradation is transmissible between silenced and non-silenced plants, but not between silenced plants

    Plant J.

    (2000)
  • G. Pruss

    Plant viral synergism: the potyviral genome encodes a broad-range pathogenicity enhancer that transactivates replication of heterologous viruses

    Plant Cell

    (1997)
  • R. Anandalakshmi

    A viral suppressor of gene silencing in plants

    Proc. Natl. Acad. Sci. U. S. A.

    (1998)
  • K.D. Kasschau et al.

    A counterdefensive strategy of plant viruses: suppression of post-transcriptional gene silencing

    Cell

    (1998)
  • G. Brigneti

    Viral pathogenicity determinants are suppressors of transgene silencing in Nicotiana benthamiana

    EMBO J.

    (1998)
  • O. Voinnet

    Suppression of gene silencing: a general strategy used by diverse DNA and RNA viruses of plants

    Proc. Natl. Acad. Sci. U. S. A.

    (1999)
  • H-W. Li

    Strong host resistance targeted against a viral suppressor of the plant gene silencing defence mechanism

    EMBO J.

    (1999)
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