Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Small RNA-based antimicrobial immunity

Abstract

Protection against microbial infection in eukaryotes is provided by diverse cellular and molecular mechanisms. Here, we present a comparative view of the antiviral activity of virus-derived small interfering RNAs in fungi, plants, invertebrates and mammals, detailing the mechanisms for their production, amplification and activity. We also highlight the recent discovery of viral PIWI-interacting RNAs in animals and a new role for mobile host and pathogen small RNAs in plant defence against eukaryotic pathogens. In turn, viruses that infect plants, insects and mammals, as well as eukaryotic pathogens of plants, have evolved specific virulence proteins that suppress RNA interference (RNAi). Together, these advances suggest that an antimicrobial function of the RNAi pathway is conserved across eukaryotic kingdoms.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Antiviral RNAi in insects and mammals.
Fig. 2: Antiviral RNAi in plants and nematodes.
Fig. 3: Regulation of antiviral RNAi in rice plants.
Fig. 4: Antimicrobial RNAi by mobile small silencing RNAs.

Similar content being viewed by others

References

  1. Ghildiyal, M. & Zamore, P. D. Small silencing RNAs: an expanding universe. Nat. Rev. Genet. 10, 94–108 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Baulcombe, D. RNA silencing in plants. Nature 431, 356–363 (2004).

    CAS  PubMed  Google Scholar 

  3. Haasnoot, J., Westerhout, E. M. & Berkhout, B. RNA interference against viruses: strike and counterstrike. Nat. Biotechnol. 25, 1435–1443 (2007).

    CAS  PubMed  Google Scholar 

  4. Ding, S. W. RNA-based antiviral immunity. Nat. Rev. Immunol. 10, 632–644 (2010).

    CAS  PubMed  Google Scholar 

  5. Qiao, Y. et al. Oomycete pathogens encode RNA silencing suppressors. Nat. Genet. 45, 330–333 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Weiberg, A. et al. Fungal small RNAs suppress plant immunity by hijacking host RNA interference pathways. Science 342, 118–123 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Zhang, T. et al. Cotton plants export microRNAs to inhibit virulence gene expression in a fungal pathogen. Nat. Plants 2, 16153 (2016). References 5–7 provide the first evidence for the RNAi pathway in the defence of host plants against eukaryotic pathogens.

    CAS  PubMed  Google Scholar 

  8. Li, Y., Lu, J., Han, Y., Fan, X. & Ding, S. W. RNA interference functions as an antiviral immunity mechanism in mammals. Science 342, 231–234 (2013).

    CAS  PubMed  Google Scholar 

  9. Maillard, P. V. et al. Antiviral RNA interference in mammalian cells. Science 342, 235–238 (2013).

    CAS  PubMed  Google Scholar 

  10. Li, Y. et al. Induction and suppression of antiviral RNA interference by influenza A virus in mammalian cells. Nat. Microbiol. 2, 16250 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Qiu, Y. et al. Human virus-derived small RNAs can confer antiviral immunity in mammals. Immunity 46, 992–1004 (2017). References 8–11 provide the first evidence for an antiviral function of the RNAi pathway in mammals.

    CAS  PubMed  Google Scholar 

  12. Goubau, D., Deddouche, S. & Reis e Sousa, C. Cytosolic sensing of viruses. Immunity 38, 855–869 (2013).

    CAS  PubMed  Google Scholar 

  13. Wu, J. & Chen, Z. J. Innate immune sensing and signaling of cytosolic nucleic acids. Annu. Rev. Immunol. 32, 461–488 (2014).

    CAS  PubMed  Google Scholar 

  14. Li, H. W., Li, W. X. & Ding, S. W. Induction and suppression of RNA silencing by an animal virus. Science 296, 1319–1321 (2002). This article demonstrates specific suppression of antiviral RNAi by a virus-encoded protein and, together with references 15 and 16, provides the first evidence for an antiviral function of the RNAi pathway in insects.

    CAS  PubMed  Google Scholar 

  15. Wang, X. H. et al. RNA interference directs innate immunity against viruses in adult Drosophila. Science 312, 452–454 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Galiana-Arnoux, D., Dostert, C., Schneemann, A., Hoffmann, J. A. & Imler, J. L. Essential function in vivo for Dicer-2 in host defense against RNA viruses in drosophila. Nat. Immunol. 7, 590–597 (2006).

    CAS  PubMed  Google Scholar 

  17. Aliyari, R. et al. Mechanism of induction and suppression of antiviral immunity directed by virus-derived small RNAs in Drosophila. Cell Host Microbe 4, 387–397 (2008). This article reports the first deep sequencing of viral siRNAs, identifying viral dsRNA replicative intermediates as the precursors.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Wu, Q. et al. Virus discovery by deep sequencing and assembly of virus-derived small silencing RNAs. Proc. Natl Acad. Sci. USA 107, 1606–1611 (2010).

    CAS  PubMed  Google Scholar 

  19. Han, Y. H. et al. RNA-based immunity terminates viral infection in adult Drosophila in the absence of viral suppression of RNA interference: characterization of viral small interfering RNA populations in wild-type and mutant flies. J. Virol. 85, 13153–13163 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Kemp, C. et al. Broad RNA interference-mediated antiviral immunity and virus-specific inducible responses in Drosophila. J. Immunol. 190, 650–658 (2013).

    CAS  PubMed  Google Scholar 

  21. Sinha, N. K., Iwasa, J., Shen, P. S. & Bass, B. L. Dicer uses distinct modules for recognizing dsRNA termini. Science 359, 329–334 (2018). This study identifies that the helicase domain of Dicer-2 is required for binding dsRNA with blunt termini.

    CAS  PubMed  Google Scholar 

  22. Lee, Y. S. et al. Distinct roles for Drosophila Dicer-1 and Dicer-2 in the siRNA/miRNA silencing pathways. Cell 117, 69–81 (2004).

    CAS  PubMed  Google Scholar 

  23. Segers, G. C., Zhang, X., Deng, F., Sun, Q. & Nuss, D. L. Evidence that RNA silencing functions as an antiviral defense mechanism in fungi. Proc. Natl Acad. Sci. USA 104, 12902–12906 (2007).

    CAS  PubMed  Google Scholar 

  24. Campo, S., Gilbert, K. B. & Carrington, J. C. Small RNA-based antiviral defense in the phytopathogenic fungus Colletotrichum higginsianum. PLOS Pathog. 12, e1005640 (2016). This paper reports a comprehensive characterization of antiviral RNAi in a fungus.

    PubMed  PubMed Central  Google Scholar 

  25. Sabin, L. R. et al. Dicer-2 processes diverse viral RNA species. PLOS ONE 8, e55458 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Mueller, S. et al. RNAi-mediated immunity provides strong protection against the negative-strand RNA vesicular stomatitis virus in Drosophila. Proc. Natl Acad. Sci. USA 107, 19390–19395 (2010).

    CAS  PubMed  Google Scholar 

  27. Vodovar, N., Goic, B., Blanc, H. & Saleh, M. C. In silico reconstruction of viral genomes from small RNAs improves virus-derived small interfering RNA profiling. J. Virol. 85, 11016–11021 (2011).

    PubMed  PubMed Central  Google Scholar 

  28. Bronkhorst, A. W. et al. The DNA virus Invertebrate iridescent virus 6 is a target of the Drosophila RNAi machinery. Proc. Natl Acad. Sci. USA 109, E3604–E3613 (2012).

    CAS  PubMed  Google Scholar 

  29. Myles, K. M., Wiley, M. R., Morazzani, E. M. & Adelman, Z. N. Alphavirus-derived small RNAs modulate pathogenesis in disease vector mosquitoes. Proc. Natl Acad. Sci. USA 105, 19938–19943 (2008).

    CAS  PubMed  Google Scholar 

  30. Samuel, G. H., Adelman, Z. N. & Myles, K. M. Antiviral immunity and virus-mediated antagonism in disease vector mosquitoes. Trends Microbiol. 5, 447–461 (2018).

    Google Scholar 

  31. Chejanovsky, N. et al. Characterization of viral siRNA populations in honey bee colony collapse disorder. Virology 454–455, 176–183 (2014).

    PubMed  Google Scholar 

  32. Santos, D. et al. Insights into RNAi-based antiviral immunity in Lepidoptera: acute and persistent infections in Bombyx mori and Trichoplusia ni cell lines. Sci. Rep. 8, 2423 (2018).

    PubMed  PubMed Central  Google Scholar 

  33. Zografidis, A. et al. Viral small-RNA analysis of bombyx mori larval midgut during persistent and pathogenic cytoplasmic polyhedrosis virus infection. J. Virol. 89, 11473–11486 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Lan, H. et al. Small interfering RNA pathway modulates persistent infection of a plant virus in its insect vector. Sci. Rep. 6, 20699 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Fu, Y. et al. The genome of the Hi5 germ cell line from Trichoplusia ni, an agricultural pest and novel model for small RNA biology. eLife 7, e31628 (2018).

    PubMed  PubMed Central  Google Scholar 

  36. Gammon, D. B. & Mello, C. C. RNA interference-mediated antiviral defense in insects. Curr. Opin. Insect Sci. 8, 111–120 (2015).

    PubMed  PubMed Central  Google Scholar 

  37. Samuel, G. H., Wiley, M. R., Badawi, A., Adelman, Z. N. & Myles, K. M. Yellow fever virus capsid protein is a potent suppressor of RNA silencing that binds double-stranded RNA. Proc. Natl Acad. Sci. USA 113, 13863–13868 (2016).

    CAS  PubMed  Google Scholar 

  38. Xie, Z. et al. Genetic and functional diversification of small RNA pathways in plants. PLOS Biol. 2, E104 (2004). This paper reports the first genetic evidence for Dicer-dependent biogenesis of virus-derived siRNAs.

    PubMed  PubMed Central  Google Scholar 

  39. Bouche, N., Lauressergues, D., Gasciolli, V. & Vaucheret, H. An antagonistic function for Arabidopsis DCL2 in development and a new function for DCL4 in generating viral siRNAs. EMBO J. 25, 3347–3356 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Fusaro, A. F. et al. RNA interference-inducing hairpin RNAs in plants act through the viral defence pathway. EMBO Rep. 7, 1168–1175 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Deleris, A. et al. Hierarchical action and inhibition of plant dicer-like proteins in antiviral defense. Science 313, 68–71 (2006).

    CAS  PubMed  Google Scholar 

  42. Diaz-Pendon, J. A., Li, F., Li, W. X. & Ding, S. W. Suppression of antiviral silencing by cucumber mosaic virus 2b protein in Arabidopsis is associated with drastically reduced accumulation of three classes of viral small interfering RNAs. Plant Cell 19, 2053–2063 (2007). This paper reports the first genetic evidence for the biogenesis of secondary virus-derived siRNAs by a host RNA-dependent RNA polymerase.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Andika, I. B. et al. Differential contributions of plant Dicer-like proteins to antiviral defences against potato virus X in leaves and roots. Plant J. 81, 781–793 (2015).

    CAS  PubMed  Google Scholar 

  44. Brosseau, C. & Moffett, P. Functional and genetic analysis identify a role for Arabidopsis ARGONAUTE5 in antiviral RNA silencing. Plant Cell 27, 1742–1754 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Garcia-Ruiz, H. et al. Arabidopsis RNA-dependent RNA polymerases and dicer-like proteins in antiviral defense and small interfering RNA biogenesis during turnip mosaic virus infection. Plant Cell 22, 481–496 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Wang, X. B. et al. RNAi-mediated viral immunity requires amplification of virus-derived siRNAs in Arabidopsis thaliana. Proc. Natl Acad. Sci. USA 107, 484–489 (2010).

    CAS  PubMed  Google Scholar 

  47. Wang, X. B. et al. The 21-nucleotide, but not 22-nucleotide, viral secondary small interfering RNAs direct potent antiviral defense by two cooperative argonautes in Arabidopsis thaliana. Plant Cell 23, 1625–1638 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Yang, X. et al. Characterization of small interfering RNAs derived from the geminivirus/betasatellite complex using deep sequencing. PLOS ONE 6, e16928 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Blevins, T. et al. Massive production of small RNAs from a non-coding region of Cauliflower mosaic virus in plant defense and viral counter-defense. Nucleic Acids Res. 39, 5003–5014 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Aregger, M. et al. Primary and secondary siRNAs in geminivirus-induced gene silencing. PLOS Pathog. 8, e1002941 (2012).

    PubMed  PubMed Central  Google Scholar 

  51. Raja, P., Jackel, J. N., Li, S., Heard, I. M. & Bisaro, D. M. Arabidopsis double-stranded RNA binding protein DRB3 participates in methylation-mediated defense against geminiviruses. J. Virol. 88, 2611–2622 (2014).

    PubMed  PubMed Central  Google Scholar 

  52. Raja, P., Sanville, B. C., Buchmann, R. C. & Bisaro, D. M. Viral genome methylation as an epigenetic defense against geminiviruses. J. Virol. 82, 8997–9007 (2008). This article reports the first evidence for an antiviral function of the RNA-directed DNA methylation pathway against a DNA virus.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Jackel, J. N., Storer, J. M., Coursey, T. & Bisaro, D. M. Arabidopsis RNA polymerases IV and V are required to establish H3K9 methylation, but not cytosine methylation, on geminivirus chromatin. J. Virol. 90, 7529–7540 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Katsarou, K., Mavrothalassiti, E., Dermauw, W., Van Leeuwen, T. & Kalantidis, K. Combined activity of DCL2 and DCL3 is crucial in the defense against Potato spindle tuber viroid. PLOS Pathog. 12, e1005936 (2016).

    PubMed  PubMed Central  Google Scholar 

  55. Ding, B. The biology of viroid-host interactions. Annu. Rev. Phytopathol. 47, 105–131 (2009).

    CAS  PubMed  Google Scholar 

  56. Navarro, B. et al. Deep sequencing of viroid-derived small RNAs from grapevine provides new insights on the role of RNA silencing in plant-viroid interaction. PLOS ONE 4, e7686 (2009).

    PubMed  PubMed Central  Google Scholar 

  57. Martinez, G., Donaire, L., Llave, C., Pallas, V. & Gomez, G. High-throughput sequencing of Hop stunt viroid-derived small RNAs from cucumber leaves and phloem. Mol. Plant Pathol. 11, 347–359 (2010).

    CAS  PubMed  Google Scholar 

  58. Wu, Q. et al. Homology-independent discovery of replicating pathogenic circular RNAs by deep sequencing and a new computational algorithm. Proc. Natl Acad. Sci. USA 109, 3938–3943 (2012).

    CAS  PubMed  Google Scholar 

  59. Lu, R. et al. Animal virus replication and RNAi-mediated antiviral silencing in Caenorhabditis elegans. Nature 436, 1040–1043 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Wilkins, C. et al. RNA interference is an antiviral defence mechanism in Caenorhabditis elegans. Nature 436, 1044–1047 (2005).

    CAS  PubMed  Google Scholar 

  61. Felix, M. A. et al. Natural and experimental infection of Caenorhabditis nematodes by novel viruses related to nodaviruses. PLOS Biol. 9, e1000586 (2011). References 59–61 demonstrate an antiviral function of the RNAi pathway in nematodes.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Guo, X., Zhang, R., Wang, J., Ding, S. W. & Lu, R. Homologous RIG-I-like helicase proteins direct RNAi-mediated antiviral immunity in C. elegans by distinct mechanisms. Proc. Natl Acad. Sci. USA 110, 16085–16090 (2013).

    CAS  PubMed  Google Scholar 

  63. Ashe, A. et al. A deletion polymorphism in the Caenorhabditis elegans RIG-I homolog disables viral RNA dicing and antiviral immunity. eLife 2, e00994 (2013).

    PubMed  PubMed Central  Google Scholar 

  64. Gammon, D. B. et al. The antiviral RNA interference response provides resistance to lethal arbovirus infection and vertical transmission in Caenorhabditis elegans. Curr. Biol. 27, 795–806 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Parameswaran, P. et al. Six RNA viruses and forty-one hosts: viral small RNAs and modulation of small RNA repertoires in vertebrate and invertebrate systems. PLOS Pathog. 6, e1000764 (2010).

    PubMed  PubMed Central  Google Scholar 

  66. Lu, R., Yigit, E., Li, W. X. & Ding, S. W. An RIG-I-Like RNA helicase mediates antiviral RNAi downstream of viral siRNA biogenesis in Caenorhabditis elegans. PLOS Pathog. 5, e1000286 (2009).

    PubMed  PubMed Central  Google Scholar 

  67. Coffman, S. R. et al. Caenorhabditis elegans RIG-I. homolog mediates antiviral RNA interference downstream of Dicer-dependent biogenesis of viral small interfering RNAs. mBio 8, e00264-17 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Tabara, H., Yigit, E., Siomi, H. & Mello, C. C. The dsRNA binding protein RDE-4 interacts with RDE-1, DCR-1, and a DExX-box helicase to direct RNAi in C-elegans. Cell 109, 861–871 (2002).

    CAS  PubMed  Google Scholar 

  69. Reich, D. P., Tyc, K. M. & Bass, B. L. C. elegans ADARs antagonize silencing of cellular dsRNAs by the antiviral RNAi pathway. Genes Dev. 32, 271–282 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Umbach, J. L., Yen, H. L., Poon, L. L. & Cullen, B. R. Influenza A virus expresses high levels of an unusual class of small viral leader RNAs in infected cells. mBio 1, e00204-10 (2010).

    PubMed  PubMed Central  Google Scholar 

  71. Perez, J. T. et al. Influenza A virus-generated small RNAs regulate the switch from transcription to replication. Proc. Natl Acad. Sci. USA 107, 11525–11530 (2010).

    CAS  PubMed  Google Scholar 

  72. Girardi, E., Chane-Woon-Ming, B., Messmer, M., Kaukinen, P. & Pfeffer, S. Identification of RNase L-dependent, 3ʹ-end-modified, viral small RNAs in Sindbis virus-infected mammalian cells. MBio 4, e00698-13 (2013).

    PubMed  PubMed Central  Google Scholar 

  73. Seo, G. J. et al. Reciprocal inhibition between intracellular antiviral signaling and the RNAi machinery in mammalian cells. Cell Host Microbe 14, 435–445 (2013).

    CAS  PubMed  Google Scholar 

  74. Bogerd, H. P. et al. Replication of many human viruses is refractory to inhibition by endogenous cellular microRNAs. J. Virol. 88, 8065–8076 (2014).

    PubMed  PubMed Central  Google Scholar 

  75. Backes, S. et al. The Mammalian response to virus infection is independent of small RNA silencing. Cell Rep. 8, 114–125 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Tanguy, M. & Miska, E. A. Antiviral RNA interference in animals: piecing together the evidence. Nat. Struct. Mol. Biol. 20, 1239–1241 (2013).

    CAS  PubMed  Google Scholar 

  77. Sagan, S. M. & Sarnow, P. Molecular biology. RNAi, antiviral after all. Science 342, 207–208 (2013).

    CAS  PubMed  Google Scholar 

  78. Li, W. X. et al. Interferon antagonist proteins of influenza and vaccinia viruses are suppressors of RNA silencing. Proc. Natl Acad. Sci. USA 101, 1350–1355 (2004). This article identifies NS1 protein of IAV as the first mammalian viral suppressor of antiviral RNAi.

    CAS  PubMed  Google Scholar 

  79. Sullivan, C. S. & Ganem, D. A virus-encoded inhibitor that blocks RNA interference in mammalian cells. J. Virol. 79, 7371–7379 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Kennedy, E. M. et al. Production of functional small interfering RNAs by an amino-terminal deletion mutant of human Dicer. Proc. Natl Acad. Sci. USA 112, E6945–E6954 (2015).

    CAS  PubMed  Google Scholar 

  81. de Vries, W., Haasnoot, J., Fouchier, R., de Haan, P. & Berkhout, B. Differential RNA silencing suppression activity of NS1 proteins from different influenza A virus strains. J. Gen. Virol. 90, 1916–1922 (2009).

    PubMed  Google Scholar 

  82. Muangsan, N., Beclin, C., Vaucheret, H. & Robertson, D. Geminivirus VIGS of endogenous genes requires SGS2/SDE1 and SGS3 and defines a new branch in the genetic pathway for silencing in plants. Plant J. 38, 1004–1014 (2004).

    CAS  PubMed  Google Scholar 

  83. Li, F., Huang, C., Li, Z. & Zhou, X. Suppression of RNA silencing by a plant DNA virus satellite requires a host calmodulin-like protein to repress RDR6 expression. PLOS Pathog. 10, e1003921 (2014).

    PubMed  PubMed Central  Google Scholar 

  84. Verlaan, M. G. et al. The Tomato Yellow Leaf Curl Virus resistance genes Ty-1 and Ty-3 are allelic and code for DFDGD-class RNA-dependent RNA polymerases. PLOS Genet. 9, e1003399 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Guo, Z. et al. Lipid flippases promote antiviral silencing and the biogenesis of viral and host siRNAs in Arabidopsis. Proc. Natl Acad. Sci. USA 114, 1377–1382 (2017).

    CAS  PubMed  Google Scholar 

  86. Zhu, B. et al. Arabidopsis ALA1 and ALA2 mediate RNAi-based antiviral immunity. Front. Plant Sci. 8, 422 (2017).

    PubMed  PubMed Central  Google Scholar 

  87. Guo, Z. et al. Identification of a new host factor required for antiviral RNAi and amplification of viral siRNAs. Plant Physiol. 176, 1587–1597 (2018).

    CAS  PubMed  Google Scholar 

  88. Xie, Z., Fan, B., Chen, C. & Chen, Z. An important role of an inducible RNA-dependent RNA polymerase in plant antiviral defense. Proc. Natl Acad. Sci. USA 98, 6516–6521 (2001).

    CAS  PubMed  Google Scholar 

  89. Leibman, D. et al. Differential expression of cucumber RNA-dependent RNA polymerase 1 genes during antiviral defence and resistance. Mol. Plant Pathol. 19, 300–312 (2018).

    CAS  PubMed  Google Scholar 

  90. Wang, H. et al. A signaling cascade from miR444 to RDR1 in rice antiviral RNA silencing pathway. Plant Physiol. 170, 2365–2377 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Long, T. & Lu, R. Northern blot detection of virus-derived small interfering RNAs in Caenorhabditis elegans using nonradioactive oligo probes. Methods Mol. Biol. 1656, 79–88 (2017).

    CAS  PubMed  Google Scholar 

  92. Goic, B. et al. RNA-mediated interference and reverse transcription control the persistence of RNA viruses in the insect model Drosophila. Nat. Immunol. 14, 396–403 (2013). This article demonstrates an antiviral function for viral DNA reverse transcribed from viral RNAs.

    CAS  PubMed  Google Scholar 

  93. Goic, B. et al. Virus-derived DNA drives mosquito vector tolerance to arboviral infection. Nat. Commun. 7, 12410 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Tassetto, M., Kunitomi, M. & Andino, R. Circulating immune cells mediate a systemic RNAi-based adaptive antiviral response in Drosophila. Cell 169, 314–325 (2017). This article identifies circulating viral siRNAs in exosome-like vesicles in fruitflies.

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Poirier, E. Z. et al. Dicer-2-dependent generation of viral DNA from defective genomes of RNA viruses modulates antiviral immunity in insects. Cell Host Microbe 23, 353–365 (2018). This article identifies the production of viral siRNAs templated by circular viral DNA reverse transcribed from viral RNAs.

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Paulsen, T., Kumar, P., Koseoglu, M. M. & Dutta, A. Discoveries of extrachromosomal circles of DNA in normal and tumor cells. Trends Genet. 34, 270–278 (2018).

    CAS  PubMed  Google Scholar 

  97. Shimizu, A. et al. Characterisation of cytoplasmic DNA complementary to non-retroviral RNA viruses in human cells. Sci. Rep. 4, 5074 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  98. 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 

  99. Hamilton, A. J. & Baulcombe, D. C. A species of small antisense RNA in posttranscriptional gene silencing in plants. Science 286, 950–952 (1999). This paper reports the first evidence for the production of virus-derived small RNAs.

    CAS  PubMed  Google Scholar 

  100. Llave, C., Xie, Z. X., Kasschau, K. D. & Carrington, J. C. Cleavage of Scarecrow-like mRNA targets directed by a class of Arabidopsis miRNA. Science 297, 2053–2056 (2002).

    CAS  PubMed  Google Scholar 

  101. Kjemtrup, S. et al. Gene silencing from plant DNA carried by a Geminivirus. Plant J. 14, 91–100 (1998).

    CAS  PubMed  Google Scholar 

  102. Guo, X., Li, W. X. & Lu, R. Silencing of host genes directed by virus-derived short interfering RNAs in Caenorhabditis elegans. J. Virol. 86, 11645–11653 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Hammond, S. M., Boettcher, S., Caudy, A. A., Kobayashi, R. & Hannon, G. J. Argonaute2, a link between genetic and biochemical analyses of RNAi. Science 293, 1146–1150 (2001).

    CAS  PubMed  Google Scholar 

  104. Martinez, J., Patkaniowska, A., Urlaub, H., Luhrmann, R. & Tuschl, T. Single-stranded antisense siRNAs guide target RNA cleavage in RNAi. Cell 110, 563–574 (2002).

    CAS  PubMed  Google Scholar 

  105. Wilson, R. C. & Doudna, J. A. Molecular mechanisms of RNA interference. Annu. Rev. Biophys. 42, 217–239 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Keene, K. M. et al. RNA interference acts as a natural antiviral response to O’nyong-nyong virus (Alphavirus; Togaviridae) infection of Anopheles gambiae. Proc. Natl Acad. Sci. USA 101, 17240–17245 (2004).

    CAS  PubMed  Google Scholar 

  107. Marques, J. T. et al. Functional specialization of the small interfering RNA pathway in response to virus infection. PLOS Pathog. 9, e1003579 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Sun, Q., Choi, G. H. & Nuss, D. L. A single Argonaute gene is required for induction of RNA silencing antiviral defense and promotes viral RNA recombination. Proc. Natl Acad. Sci. USA 106, 17927–17932 (2009).

    CAS  PubMed  Google Scholar 

  109. Morel, J. B. et al. Fertile hypomorphic ARGONAUTE (ago1) mutants impaired in post-transcriptional gene silencing and virus resistance. Plant Cell 14, 629–639 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Carbonell, A. et al. Functional analysis of three Arabidopsis ARGONAUTES using slicer-defective mutants. Plant Cell 24, 3613–3629 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Qu, F., Ye, X. & Morris, T. J. Arabidopsis DRB4, AGO1, AGO7, and RDR6 participate in a DCL4-initiated antiviral RNA silencing pathway negatively regulated by DCL1. Proc. Natl Acad. Sci. USA 105, 14732–14737 (2008).

    CAS  PubMed  Google Scholar 

  112. Wu, J. et al. Viral-inducible Argonaute18 confers broad-spectrum virus resistance in rice by sequestering a host microRNA. eLife 4, e05733 (2015). This article reveals a new antiviral function for AGO proteins by derepressing antiviral RNAi.

    PubMed Central  Google Scholar 

  113. Alazem, M., He, M. H., Moffett, P. & Lin, N. S. Abscisic acid induces resistance against Bamboo mosaic virus through Argonaute2 and 3. Plant Physiol. 174, 339–355 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Liu, Q. et al. R2D2, a bridge between the initiation and effector steps of the Drosophila RNAi pathway. Science 301, 1921–1925 (2003).

    CAS  PubMed  Google Scholar 

  115. Liu, J. et al. Argonaute2 is the catalytic engine of mammalian RNAi. Science 305, 1437–1441 (2004).

    CAS  PubMed  Google Scholar 

  116. Schuck, J., Gursinsky, T., Pantaleo, V., Burgyan, J. & Behrens, S. E. AGO/RISC-mediated antiviral RNA silencing in a plant in vitro system. Nucleic Acids Res. 41, 5090–5103 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Cheloufi, S., Dos Santos, C. O., Chong, M. M. & Hannon, G. J. A dicer-independent miRNA biogenesis pathway that requires Ago catalysis. Nature 465, 584–589 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  118. O’Carroll, D. et al. A Slicer-independent role for Argonaute 2 in hematopoiesis and the microRNA pathway. Genes Dev. 21, 1999–2004 (2007).

    PubMed  PubMed Central  Google Scholar 

  119. Maillard, P. V. et al. Inactivation of the type I interferon pathway reveals long double-stranded RNA-mediated RNA interference in mammalian cells. EMBO J. 35, 2505–2518 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Tsai, K., Courtney, D. G., Kennedy, E. M. & Cullen, B. R. Influenza A virus-derived siRNAs increase in the absence of NS1 yet fail to inhibit virus replication. RNA 24, 1172–1182 (2018).

    CAS  PubMed  Google Scholar 

  121. Dzianott, A., Sztuba-Solinska, J. & Bujarski, J. J. Mutations in the antiviral RNAi defense pathway modify Brome mosaic virus RNA recombinant profiles. Mol. Plant Microbe Interact. 25, 97–106 (2012).

    CAS  PubMed  Google Scholar 

  122. Korner, C. J. et al. Crosstalk between PTGS and TGS pathways in natural antiviral immunity and disease recovery. Nat. Plants 4, 157–164 (2018).

    PubMed  Google Scholar 

  123. Vaucheret, H., Vazquez, F., Crete, P. & Bartel, D. P. The action of ARGONAUTE1 in the miRNA pathway and its regulation by the miRNA pathway are crucial for plant development. Genes Dev. 18, 1187–1197 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Brodersen, P. et al. Widespread translational inhibition by plant mi-RNAs and siRNAs. Science 320, 1185–1190 (2008).

    CAS  PubMed  Google Scholar 

  125. Li, S. et al. Biogenesis of phased siRNAs on membrane-bound polysomes in Arabidopsis. eLife 5, e22750 (2016).

    PubMed  PubMed Central  Google Scholar 

  126. Ghoshal, B. & Sanfacon, H. Temperature-dependent symptom recovery in Nicotiana benthamiana plants infected with tomato ringspot virus is associated with reduced translation of viral RNA2 and requires ARGONAUTE 1. Virology 456–457, 188–197 (2014).

    PubMed  Google Scholar 

  127. Fatyol, K., Ludman, M. & Burgyan, J. Functional dissection of a plant Argonaute. Nucleic Acids Res. 44, 1384–1397 (2016).

    CAS  PubMed  Google Scholar 

  128. Petrillo, J. E. et al. Cytoplasmic granule formation and translational inhibition of nodaviral RNAs in the absence of the double-stranded RNA binding protein B2. J. Virol. 87, 13409–13421 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Chao, J. A. et al. Dual modes of RNA-silencing suppression by Flock House virus protein B2. Nat. Struct. Mol. Biol. 12, 952–957 (2005).

    CAS  PubMed  Google Scholar 

  130. Vaucheret, H., Mallory, A. C. & Bartel, D. P. AGO1 homeostasis entails coexpression of MIR168 and AGO1 and preferential stabilization of miR168 by AGO1. Mol. Cell 22, 129–136 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Al Kaff, N. S. et al. Transcriptional and posttranscriptional plant gene silencing in response to a pathogen. Science 279, 2113–2115 (1998).

    CAS  PubMed  Google Scholar 

  132. Seemanpillai, M., Dry, I., Randles, J. & Rezaian, A. Transcriptional silencing of geminiviral promoter-driven transgenes following homologous virus infection. Mol. Plant Microbe Interact. 16, 429–438 (2003).

    CAS  PubMed  Google Scholar 

  133. Raja, P., Wolf, J. N. & Bisaro, D. M. RNA silencing directed against geminiviruses: post-transcriptional and epigenetic components. Biochim. Biophys. Acta 1799, 337–351 (2010).

    CAS  PubMed  Google Scholar 

  134. Coursey, T., Regedanz, E. & Bisaro, D. M. Arabidopsis RNA polymerase V mediates enhanced compaction and silencing of geminivirus and transposon chromatin during host recovery from infection. J. Virol. 92, e01320-17 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  135. Wendte, J. M. & Pikaard, C. S. The RNAs of RNA-directed DNA methylation. Biochim. Biophys. Acta 1860, 140–148, (2017).

    Google Scholar 

  136. Ding, S. W., Han, Q., Wang, J. & Li, W. X. Antiviral RNA interference in mammals. Curr. Opin. Immunol. 54, 109–114 (2018).

    CAS  PubMed  Google Scholar 

  137. Csorba, T., Kontra, L. & Burgyan, J. Viral silencing suppressors: tools forged to fine-tune host-pathogen coexistence. Virology 479–480, 85–103 (2015).

    PubMed  Google Scholar 

  138. Kasschau, K. D. & Carrington, J. C. A counterdefensive strategy of plant viruses: suppression of posttranscriptional gene silencing. Cell 95, 461–470 (1998).

    CAS  PubMed  Google Scholar 

  139. Anandalakshmi, R. et al. A viral suppressor of gene silencing in plants. Proc. Natl Acad. Sci. USA 95, 13079–13084 (1998).

    CAS  PubMed  Google Scholar 

  140. 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 

  141. Lichner, Z., Silhavy, D. & Burgyan, J. Double-stranded RNA-binding proteins could suppress RNA interference-mediated antiviral defences. J. Gen. Virol. 84, 975–980 (2003).

    CAS  PubMed  Google Scholar 

  142. Johansen, L. K. & Carrington, J. C. Silencing on the spot. Induction and suppression of RNA silencing in the Agrobacterium-mediated transient expression system. Plant Physiol. 126, 930–938 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  143. Zhang, X. P. et al. Cucumber mosaic virus coat protein modulates the accumulation of 2b protein and antiviral silencing that causes symptom recovery in planta. PLOS Pathog. 13, e1006522 (2017).

    PubMed  PubMed Central  Google Scholar 

  144. Guo, H. S. & Ding, S. W. A viral protein inhibits the long range signaling activity of the gene silencing signal. EMBO J. 21, 398–407 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  145. Rosas-Diaz, T. et al. A virus-targeted plant receptor-like kinase promotes cell-to-cell spread of RNAi. Proc. Natl Acad. Sci. USA 115, 1388–1393 (2018).

    CAS  PubMed  Google Scholar 

  146. Incarbone, M. et al. Neutralization of mobile antiviral small RNA through peroxisomal import. Nat. Plants 3, 17094 (2017).

    CAS  PubMed  Google Scholar 

  147. Melnyk, C. W., Molnar, A. & Baulcombe, D. C. Intercellular and systemic movement of RNA silencing signals. EMBO J. 30, 3553–3563 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  148. Taochy, C. et al. A genetic screen for impaired systemic RNAi highlights the crucial role of DICER-LIKE 2. Plant Physiol. 175, 1424–1437 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  149. Chen, W. et al. A genetic network for systemic RNA silencing in plants. Plant Physiol. 176, 2700–2719 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  150. Jee, D. et al. Dual strategies for Argonaute2-mediated biogenesis of erythroid mi-RNAs underlie conserved requirements for slicing in mammals. Mol. Cell 69, 265–278 (2018).

    CAS  PubMed  Google Scholar 

  151. Morazzani, E. M., Wiley, M. R., Murreddu, M. G., Adelman, Z. N. & Myles, K. M. Production of virus-derived ping-pong-dependent piRNA-like small RNAs in the mosquito soma. PLOS Pathog. 8, e1002470 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  152. Dietrich, I. et al. RNA interference restricts Rift Valley Fever Virus in multiple insect systems. mSphere 2, e00090-17 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  153. Miesen, P., Joosten, J. & van Rij, R. P. PIWIs go viral: arbovirus-derived piRNAs in vector mosquitoes. PLOS Pathog. 12, e1006017 (2016).

    PubMed  PubMed Central  Google Scholar 

  154. Aguiar, E. R. et al. Sequence-independent characterization of viruses based on the pattern of viral small RNAs produced by the host. Nucleic Acids Res. 43, 6191–6206 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  155. Arensburger, P., Hice, R. H., Wright, J. A., Craig, N. L. & Atkinson, P. W. The mosquito Aedes aegypti has a large genome size and high transposable element load but contains a low proportion of transposon-specific piRNAs. BMC Genomics 12, 606 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  156. Parrish, N. F. et al. piRNAs derived from ancient viral processed pseudogenes as transgenerational sequence-specific immune memory in mammals. RNA 21, 1691–1703 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  157. Sun, Y. H. et al. Domestic chickens activate a piRNA defense against avian leukosis virus. eLife 6, e24695 (2017).

    PubMed  PubMed Central  Google Scholar 

  158. Whitfield, Z. J. et al. The diversity, structure, and function of heritable adaptive immunity sequences in the Aedes aegypti genome. Curr. Biol. 27, 3511–3519 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  159. Varjak, M. et al. Aedes aegypti Piwi4 is a noncanonical PIWI protein involved in antiviral responses. mSphere 2, e00144-17 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  160. Miesen, P., Girardi, E. & van Rij, R. P. Distinct sets of PIWI proteins produce arbovirus and transposon-derived piRNAs in Aedes aegypti mosquito cells. Nucleic Acids Res. 43, 6545–6556 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  161. Schnettler, E. et al. Knockdown of piRNA pathway proteins results in enhanced Semliki Forest virus production in mosquito cells. J. Gen. Virol. 94, 1680–1689 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  162. Xiong, Q. et al. Phytophthora suppressor of RNA silencing 2 is a conserved RxLR effector that promotes infection in soybean and Arabidopsis thaliana. Mol. Plant Microbe Interact. 27, 1379–1389 (2014).

    PubMed  Google Scholar 

  163. Qiao, Y., Shi, J., Zhai, Y., Hou, Y. & Ma, W. Phytophthora effector targets a novel component of small RNA pathway in plants to promote infection. Proc. Natl Acad. Sci. USA 112, 5850–5855 (2015).

    CAS  PubMed  Google Scholar 

  164. Wong, J. et al. Roles of small RNAs in soybean defense against Phytophthora sojae infection. Plant J. 79, 928–940 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  165. Cai, Q. et al. Plants send small RNAs in extracellular vesicles to fungal pathogen to silence virulence genes. Science 360, 1126–1129 (2018). This article reports a role for exosome-like vesicles in the export of plant endogenous siRNAs to fungal cells for gene silencing.

    CAS  PubMed  Google Scholar 

  166. Nowara, D. et al. HIGS: host-induced gene silencing in the obligate biotrophic fungal pathogen Blumeria graminis. Plant Cell 22, 3130–3141 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  167. Shahid, S. et al. MicroRNAs from the parasitic plant Cuscuta campestris target host messenger RNAs. Nature 553, 82–85 (2018).

    CAS  PubMed  Google Scholar 

  168. Urbach, J. M. & Ausubel, F. M. The NBS-LRR architectures of plant R-proteins and metazoan NLRs evolved in independent events. Proc. Natl Acad. Sci. USA 114, 1063–1068 (2017).

    CAS  PubMed  Google Scholar 

  169. Ausubel, F. M. Are innate immune signaling pathways in plants and animals conserved? Nat. Immunol. 6, 973–979 (2005).

    CAS  PubMed  Google Scholar 

  170. Kollmann, T. R., Levy, O., Montgomery, R. R. & Goriely, S. Innate immune function by Toll-like receptors: distinct responses in newborns and the elderly. Immunity 37, 771–783 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  171. Girardi, E. et al. Cross-species comparative analysis of Dicer proteins during Sindbis virus infection. Sci. Rep. 5, 10693 (2015).

    PubMed  PubMed Central  Google Scholar 

  172. Kennedy, E. M., Kornepati, A. V., Bogerd, H. P. & Cullen, B. R. Partial reconstitution of the RNAi response in human cells using Drosophila gene products. RNA 23, 153–160 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  173. Schuster, S., Tholen, L. E., Overheul, G. J., van Kuppeveld, F. J. M. & van Rij, R. P. Deletion of cytoplasmic double-stranded RNA sensors does not uncover viral small interfering RNA production in human cells. mSphere 2, e00333-317 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  174. van der Veen, A. G. et al. The RIG-I-like receptor LGP2 inhibits Dicer-dependent processing of long double-stranded RNA and blocks RNA interference in mammalian cells. EMBO J. 37, e97479 (2018).

    PubMed  PubMed Central  Google Scholar 

  175. Haasnoot, J. & Berkhout, B. RNA Towards Medicine (eds Erdmann, V., Barciszewski, J. & Brosius, J.) 117–150 (2006).

  176. Bastin, D. et al. Enhanced susceptibility of cancer cells to oncolytic rhabdo-virotherapy by expression of Nodamura virus protein B2 as a suppressor of RNA interference. J. Immunother. Cancer 6, 62 (2018).

    PubMed  PubMed Central  Google Scholar 

  177. Li, F. & Ding, S. W. Virus counterdefense: diverse strategies for evading the RNA-silencing immunity. Annu. Rev. Microbiol. 60, 503–531 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  178. Guo, X. & Lu, R. Characterization of virus-encoded RNA interference suppressors in Caenorhabditis elegans. J. Virol. 87, 5414–5423 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors acknowledge research support by grants from the US National Institute of Allergy and Infectious Diseases and National Institute of General Medical Sciences, the US Department of Agriculture and the Agricultural Experimental Station of the University of California, Riverside (to S.-W.D.), the Fujian Agriculture and Forestry University (to Z.G.) and the National Natural Science Foundation of China (to Y.L.). Because of space limitations, the authors have often cited reviews rather than primary research papers. They apologize to those investigators whose original papers have not been cited.

Author information

Authors and Affiliations

Authors

Contributions

All authors contributed to researching the content for the manuscript and editing before submission. S.-W.D. was responsible for writing the manuscript.

Corresponding author

Correspondence to Shou-Wei Ding.

Ethics declarations

Competing interests

S.-W.D and Y.L. declare competing interests. They are named on one patent application, which is pending, regarding the use of small interfering RNAs as a new mechanism of mammalian antiviral immunity.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Glossary

Small interfering RNAs

(siRNAs). Short double-stranded RNAs of 20–23 nucleotides in length with 2-nucleotide 3′ overhangs that have 5′-monophosphate and 3′-hydroxyl termini and are cleaved from long perfectly complementary double-stranded RNA precursors by Dicer. The guide strand of siRNA in the RNA-induced silencing complex directs RNA interference in a sequence-specific manner.

microRNAs

(miRNAs). Small (~21–23 nucleotides in length), single-stranded RNA molecules that have 5′-monophosphate and 3′-hydroxyl termini, are cleaved from long hairpin RNA precursors by Dicer, and specifically inhibit gene expression in the RNA-induced silencing complex in a sequence-specific manner.

PIWI-interacting RNAs

(piRNAs). Single-stranded RNAs of 23–33 nucleotides in length that have 5′-monophosphate and 3′-hydroxyl termini and are produced from single-stranded RNA precursors in a Dicer-independent manner. They are found in animals and not in plants, possibly because plant genomes do not encode any Argonaute (AGO) protein of the PIWI subfamily that is necessary for piRNA biogenesis. piRNAs guide specific cleavages of target RNAs by PIWI proteins.

Argonaute protein

(AGO protein). A member of a family of proteins that associate with small interfering RNAs, microRNAs or PIWI-interacting RNAs to mediate RNA interference. AGO proteins contain an amino-terminal PAZ domain and a central domain that bind the 3′ end and 5′ phosphate of the guide strand small RNA, respectively, as well as a carboxy-terminal PIWI domain that has structural similarity to RNase H. A subset of AGO proteins have endonuclease activity, whereas most mammalian AGO subfamily members only silence translation.

RNA interference

(RNAi). A process of RNA sequence homology-dependent gene silencing guided by small silencing RNAs such as small interfering RNAs, microRNAs or PIWI-interacting RNAs bound to an Argonaute (AGO) protein-containing multicomponent ribonucleoprotein complex.

RNA-induced silencing complex

(RISC). A multicomponent ribonucleoprotein complex, comprising the guide strand of microRNAs or small interfering RNAs, Argonaute (AGO) proteins and cofactors, that silences the expression of proteins from target mRNAs by either RNA cleavage or RNA decay and/or translational repression depending on the complementarity of mRNA sequences to the packaged small RNAs.

IMD signalling

One of two innate immune nuclear factor-κB signalling pathways in Drosophila melanogaster. The IMD pathway responds to DAP-type peptidoglycan from Gram-negative, and some Gram-positive, bacteria. This leads to the rapid and robust production of antimicrobial peptides.

MIKCC-type MADS box proteins

A group of transcription factors that contain the MADS box, which is involved in DNA binding and dimerization with other MADS box proteins, and three additional conserved domains — the intervening domain, the keratin domain and the carboxy-terminal domain.

Retrotransposons

A subclass of transposons that amplify themselves in a genome through a process that involves the reverse transcription of RNA to DNA by a reverse transcriptase that is encoded by a retrotransposon.

Transposons

Also known as ‘jumping genes’ and ‘selfish DNA’; DNA sequences that encode transposases, the enzymes that are required to excise the transposon from its original chromosomal location and to integrate it in a different position within the genome. The ends of transposons consist of DNA repeats that function as recognition sites for the transposase itself.

Haemocytes

Cells found within the haemolymph of an insect that are equivalent to the blood cells in vertebrates. Different types of haemocyte are plasmatocytes, crystal cells and lamellocytes. These cells have important roles in immunity through the secretion of cytokines and the phagocytic clearance of invaders.

RNA slicing

The specific endonucleolytic cleavage of mRNA molecules that contain a sequence complementary to the guide strand small RNA (small interfering RNA, microRNA or PIWI-interacting RNA) in the RNA-induced silencing complex by the PIWI domain of a subset of Argonaute (AGO) proteins. The cleavage occurs in the middle of the region that is base paired with the guide strand.

Protein kinase R

One of the cytosolic sensors of viral and artificial double-stranded RNA in mammals, which, upon activation, can phosphorylate the eukaryotic translation initiation factor eIF2α, leading to global translation shutdown and apoptosis.

Ping-pong amplification

A model proposed for the biogenesis of animal primary and secondary PIWI-interacting RNAs.

Oomycete pathogens

A distinct phylogenetic lineage of filamentous fungus-like eukaryotic microorganisms, which include important plant pathogens such as those that cause devastating diseases of potato plants.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Guo, Z., Li, Y. & Ding, SW. Small RNA-based antimicrobial immunity. Nat Rev Immunol 19, 31–44 (2019). https://doi.org/10.1038/s41577-018-0071-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41577-018-0071-x

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing