Skip to main content

Thank you for visiting 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.

Small RNAs are on the move


A key feature of RNA interference is its ability to spread from cell to cell. Such non-cell-autonomous gene silencing has been characterized extensively in both plants and animals, but the identity of the mobile silencing signal has remained elusive. Several recent studies now shed light on the identity of this signal in plants, and indicate that small RNA molecules—from short-interfering RNAs to microRNAs—are capable of moving between cells and through the vasculature. The movement of small, 21–24-nucleotide RNA species has implications for biological processes ranging from developmental patterning and stress responses to epigenetic inheritance.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: siRNA duplexes form the mobile silencing signal.
Figure 2: TAS3- derived tasiR-ARFs form a short-range mobile silencing signal.
Figure 3: Mobile siRNAs mediate graft-transmissible epigenetic silencing.


  1. 1

    Voinnet, O. & Baulcombe, D. C. Systemic signaling in gene silencing. Nature 389, 553 (1997)

    ADS  CAS  Article  Google Scholar 

  2. 2

    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  Article  Google Scholar 

  3. 3

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

    ADS  CAS  Article  Google Scholar 

  4. 4

    Timmons, L. & Fire, A. Specific interference by ingested dsRNA. Nature 395, 854 (1998)

    ADS  CAS  Article  Google Scholar 

  5. 5

    Schwach, F., Vaistij, F. E., Jones, L. & Baulcombe, D. C. An RNA-dependent RNA polymerase prevents meristem invasion by potato virus X and is required for the activity but not the production of a systemic silencing signal. Plant Physiol. 138, 1842–1852 (2005)

    CAS  Article  Google Scholar 

  6. 6

    Pant, B. D., Buhtz, A., Kehr, J. & Scheible, W. R. MicroRNA399 is a long-distance signal for the regulation of plant phosphate homeostasis. Plant J. 53, 731–738 (2008)

    CAS  Article  Google Scholar 

  7. 7

    Buhtz, A., Springer, F., Chappell, L., Baulcombe, D. C. & Kehr, J. Identification and characterization of small RNAs from the phloem of Brassica napus . Plant J. 53, 739–749 (2008)

    CAS  Article  Google Scholar 

  8. 8

    Chitwood, D. H. et al. Pattern formation via small RNA mobility. Genes Dev. 23, 549–554 (2009)This work documents the movement of endogenous ta-siRNAs by observing their accumulation outside the region of their biogenesis and proposes that gradients of small RNAs pattern gene expression through dose-dependent activity.

    CAS  Article  Google Scholar 

  9. 9

    Carlsbecker, A. et al. Cell signaling by microRNA165/6 directs gene dose-dependent root cell fate. Nature 465, 316–321 (2010)By localizing the accumulation and activity of miR165/6 and studying the expression of its precursors and targets, this work proposes that radial patterning in the root results from cell to cell movement of an miRNA and a transcription factor.

    ADS  CAS  Article  Google Scholar 

  10. 10

    Himber, C., Dunoyer, P., Moissiard, G., Ritzenthaler, C. & Voinnet, O. Transitivity-dependent and -independent cell-to-cell movement of RNA silencing. EMBO J. 22, 4523–4533 (2003)

    CAS  Article  Google Scholar 

  11. 11

    Dunoyer, P., Himber, C. & Voinnet, O. DICER-LIKE4 is required for RNA interference and produces the 21-nucleotide small interfering RNA component of the plant cell-to-cell silencing signal. Nature Genet. 37, 1356–1360 (2005)

    CAS  Article  Google Scholar 

  12. 12

    Dunoyer, D., Himber, C., Ruiz-Ferrer, V., Alioua, A. & Voinnet, O. Intra- and intercellular RNA interference in Arabidopsis thaliana requires components of the microRNA and heterochromatic silencing pathways. Nature Genet. 39, 848–856 (2007)

    CAS  Article  Google Scholar 

  13. 13

    Smith, L. M. et al. An SNF2 protein associated with nuclear RNA silencing and the spread of a silencing signal between cells in Arabidopsis . Plant Cell 19, 1507–1521 (2007)

    CAS  Article  Google Scholar 

  14. 14

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

    CAS  Article  Google Scholar 

  15. 15

    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  Article  Google Scholar 

  16. 16

    Kobayashi, K. & Zambryski, P. RNA silencing and its cell-to-cell spread during Arabidopsis embryogenesis. Plant J. 50, 597–604 (2007)

    CAS  Article  Google Scholar 

  17. 17

    Dunoyer, P. et al. Small RNA duplexes function as mobile silencing signals between plant cells. Science 328, 912–916 (2010)The authors use transgenic chimaeras to show that small RNAs form the mobile silencing signal, and on the basis of bombardment assays they conclude that the signal consists specifically of siRNA duplexes.

    ADS  CAS  Article  Google Scholar 

  18. 18

    Vargason, J. M., Szittya, G., Burgyan, J. & Hall, T. M. Size selective recognition of siRNA by an RNA silencing suppressor. Cell 115, 799–811 (2003)

    CAS  Article  Google Scholar 

  19. 19

    Montgomery, T. A. et al. Specificity of ARGONAUTE7-miR390 interaction and dual functionality in TAS3 trans-acting siRNA formation. Cell 133, 128–141 (2008)

    CAS  Article  Google Scholar 

  20. 20

    Levine, E., McHale, P. & Levine, H. Small regulatory RNAs may sharpen spatial expression patterns. PLoS Comput. Biol. 3, e233 (2007)

    ADS  MathSciNet  Article  Google Scholar 

  21. 21

    Mi, S. et al. Sorting of small RNAs in Arabidopsis argonaute complexes is directed by the 5′ terminal nucleotide. Cell 133, 116–127 (2008)

    CAS  Article  Google Scholar 

  22. 22

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

    ADS  CAS  Article  Google Scholar 

  23. 23

    Chapman, E. J. & Carrington, J. C. Specialization and evolution of endogenous small RNA pathways. Nature Rev. Genet. 8, 884–896 (2007)

    CAS  Article  Google Scholar 

  24. 24

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

    ADS  CAS  Article  Google Scholar 

  25. 25

    Molnar, A. et al. Small silencing RNAs in plants are mobile and direct epigenetic modification in recipient cells. Science 328, 872–875 (2010)Through the use of grafting and next-generation sequencing, this paper catalogues the movement of endogenous siRNAs, demonstrating that they can initiate methylation of target loci in recipient graft tissue.

    ADS  CAS  Article  Google Scholar 

  26. 26

    Baurle, I., Smith, L., Baulcombe, D. C. & Dean, C. Widespread role for the flowering-time regulators FCA and FPA in RNA-mediated chromatin silencing. Science 318, 109–112 (2007)

    ADS  Article  Google Scholar 

  27. 27

    Borsani, O., Zhu, J., Verslues, P. E., Sunkar, R. & Zhu, J. K. Endogenous siRNAs derived from a pair of natural cis-antisense transcripts regulate salt tolerance in Arabidopsis . Cell 123, 1279–1291 (2005)

    CAS  Article  Google Scholar 

  28. 28

    Slotkin, R. K. et al. Epigenetic reprogramming and small RNA silencing of transposable elements in pollen. Cell 136, 461–472 (2009)

    CAS  Article  Google Scholar 

  29. 29

    Malone, C. D. & Hannon, G. J. Small RNAs as guardians of the genome. Cell 136, 656–668 (2009)

    CAS  Article  Google Scholar 

  30. 30

    Mosher, R. A. et al. Uniparental expression of PolIV-dependent siRNAs in developing endosperm of Arabidopsis . Nature 460, 283–286 (2009)

    ADS  CAS  Article  Google Scholar 

  31. 31

    Dunoyer, P. et al. An endogenous, systemic RNAi pathway in plants. EMBO J. 29, 1699–1712 (2010)

    CAS  Article  Google Scholar 

  32. 32

    Yoo, B. C. et al. A systemic small RNA signaling system in plants. Plant Cell 16, 1979–2000 (2004)

    CAS  Article  Google Scholar 

  33. 33

    Alvarez, J. P. et al. Endogenous and synthetic microRNAs stimulate simultaneous, efficient, and localized regulation of multiple targets in diverse species. Plant Cell 18, 1134–1151 (2006)

    CAS  Article  Google Scholar 

  34. 34

    Parizotto, E. A., Dunoyer, P., Rahm, N., Himber, C. & Voinnet, O. In vivo investigation of the transcription, processing, endonucleolytic activity, and functional relevance of the spatial distribution of a plant miRNA. Genes Dev. 18, 2237–2242 (2004)

    CAS  Article  Google Scholar 

  35. 35

    Schwab, R., Ossowski, S., Riester, M., Warthmann, N. & Weigel, D. Highly specific gene silencing by artificial microRNAs in Arabidopsis . Plant Cell 18, 1121–1133 (2006)

    CAS  Article  Google Scholar 

  36. 36

    Tretter, E. M., Alvarez, J. P., Eshed, Y. & Bowman, J. L. Activity range of Arabidopsis small RNAs derived from different biogenesis pathways. Plant Physiol. 147, 58–62 (2008)

    CAS  Article  Google Scholar 

  37. 37

    Valadi, H. et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nature Cell Biol. 9, 654–659 (2007)

    CAS  Article  Google Scholar 

  38. 38

    Ruvkun, G. The perfect storm of tiny RNAs. Nature Med. 14, 1041–1045 (2008)

    CAS  Article  Google Scholar 

  39. 39

    Havecker, E. R. et al. The Arabidopsis RNA-directed DNA methylation ARGONAUTES functionally diverge based on their expression and interaction with target loci. Plant Cell 22, 321–334 (2010)

    CAS  Article  Google Scholar 

  40. 40

    Tucker, M. R. et al. Vascular signaling mediated by ZWILLE potentiates WUSCHEL function during shoot meristem stem cell development in the Arabidopsis embryo. Development 135, 2839–2843 (2008)

    CAS  Article  Google Scholar 

  41. 41

    Park, M. Y., Wu, G., Gonzalez-Sulser, A., Vaucheret, H. & Poethig, R. S. Nuclear processing and export of microRNAs in Arabidopsis . Proc. Natl Acad. Sci. USA 102, 3691–3696 (2005)

    ADS  CAS  Article  Google Scholar 

  42. 42

    Liu, Q. et al. The ARGONAUTE10 gene modulates shoot apical meristem maintenance and leaf polarity establishment by repressing miR165/6 in Arabidopsis . Plant J. 58, 27–40 (2008)

    Article  Google Scholar 

Download references


We thank current and former members of the Timmermans laboratory for discussions. Research on small RNA mobility in the laboratory of M.C.P.T. is supported by a grant from the NSF (IOS-0615752).

Author information



Corresponding author

Correspondence to Marja C. P. Timmermans.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Chitwood, D., Timmermans, M. Small RNAs are on the move. Nature 467, 415–419 (2010).

Download citation

Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


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