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.

  • Letter
  • Published:

Transposon silencing in the Caenorhabditis elegans germ line by natural RNAi

Nature volume 426, pages 310–314 (2003)Cite this article

Abstract

Transposable elements are stretches of DNA that can move and multiply within the genome of an organism. The Caenorhabditis elegans genome contains multiple Tc1 transposons that jump in somatic cells, but are silenced in the germ line1,2,3. Many mutants that have lost this silencing have also lost the ability to execute RNA interference (RNAi)2,3, a process whereby genes are suppressed by exposure to homologous double-stranded RNA (dsRNA). Here we show how RNAi causes transposon silencing in the nematode germ line. We find evidence for transposon-derived dsRNAs, in particular to the terminal inverted repeats, and show that these RNAs may derive from read-through transcription of entire transposable elements. Small interfering RNAs of Tc1 were detected. When a germline-expressed reporter gene is fused to a stretch of Tc1 sequence, this transgene is silenced in a manner dependent on functional mutator genes (mut-7, mut-16 and pk732). These results indicate that RNAi surveillance is triggered by fortuitous read-through transcription of dispersed Tc1 copies, which can form dsRNA as a result of ‘snap-back’ of the terminal inverted repeats. RNAi mediated by this dsRNA silences transposase gene expression.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1: Analyses of Tc1 RNAs.
Figure 2: Analysis of Tc1 siRNAs.
Figure 3: Trans-inactivation of Tc1-containing transgenes.

Similar content being viewed by others

References

  1. Emmons, S. W., Yesner, L., Ruan, K. S. & Katzenberg, D. Evidence for a transposon in Caenorhabditis elegans. Cell 32, 55–65 (1983)

    Article  CAS  Google Scholar 

  2. Ketting, R. F., Haverkamp, T. H., van Luenen, H. G. & Plasterk, R. H. Mut-7 of C. elegans, required for transposon silencing and RNA interference, is a homolog of Werner syndrome helicase and RNaseD. Cell 99, 133–141 (1999)

    Article  CAS  Google Scholar 

  3. Tabara, H. et al. The rde-1 gene, RNA interference, and transposon silencing in C. elegans. Cell 99, 123–132 (1999)

    Article  CAS  Google Scholar 

  4. Fischer, S. E. J., Wienholds, E. & Plasterk, R. H. A. Continuous exchange of sequence information between dispersed Tc1 transposons in the C. elegans genome. Genetics 164, 127–134 (2003)

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Vos, J. C., De Baere, I. & Plasterk, R. H. Transposase is the only nematode protein required for in vitro transposition of Tc1. Genes Dev. 10, 755–761 (1996)

    Article  CAS  Google Scholar 

  6. Plasterk, R. H. RNA silencing: the genome's immune system. Science 296, 1263–1265 (2002)

    Article  ADS  CAS  Google Scholar 

  7. Sijen, T. et al. Transcriptional and posttranscriptional gene silencing are mechanistically related. Curr. Biol. 11, 1–20 (2001)

    Article  Google Scholar 

  8. Aroian, R. V., Field, C., Pruliere, G., Kenyon, C. & Alberts, B. M. Isolation of actin-associated proteins from Caenorhabditis elegans oocytes and their localization in the early embryo. EMBO J. 16, 1541–1549 (1997)

    Article  CAS  Google Scholar 

  9. Knight, S. W. & Bass, B. L. The role of RNA editing by ADARs in RNAi. Mol. Cell 10, 809–817 (2002)

    Article  CAS  Google Scholar 

  10. 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)

    Article  ADS  CAS  Google Scholar 

  11. Sijen, T. et al. On the role of RNA amplification in dsRNA-triggered gene silencing. Cell 107, 465–476 (2001)

    Article  CAS  Google Scholar 

  12. Ambros, V., Lee, R. C., Lavanway, A., Williams, P. T. & Jewell, D. MicroRNAs and other tiny endogenous RNAs in C. elegans. Curr. Biol. 13, 807–818 (2003)

    Article  CAS  Google Scholar 

  13. Caudy, A. A. et al. A micrococcal nuclease homologue in RNAi effector complexes. Nature 425, 411–414 (2003)

    Article  ADS  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  15. Vastenhouw, N. L. et al. A genome-wide screen identifies 27 genes involved in transposon silencing in C. elegans. Curr. Biol. 13, 1311–1316 (2003)

    Article  CAS  Google Scholar 

  16. Tijsterman, M., Ketting, R. F., Okihara, K. L., Sijen, T. & Plasterk, R. H. RNA helicase MUT-14-dependent gene silencing triggered in C. elegans by short antisense RNAs. Science 295, 694–697 (2002)

    Article  ADS  CAS  Google Scholar 

  17. 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)

    Article  CAS  Google Scholar 

  18. English, J. J., Mueller, E. & Baulcombe, D. C. Suppression of virus accumulation in transgenic plants exhibiting silencing of nuclear genes. Plant Cell 8, 179–188 (1996)

    Article  CAS  Google Scholar 

  19. Sijen, T., Wellink, J., Hiriart, J. B. & Van Kammen, A. RNA-mediated virus resistance: role of repeated transgenes and delineation of targeted regions. Plant Cell 8, 2277–2294 (1996)

    Article  CAS  Google Scholar 

  20. Volpe, T. A. et al. Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science 297, 1833–1837 (2002)

    Article  ADS  CAS  Google Scholar 

  21. Reinhart, B. J. & Bartel, D. P. Small RNAs correspond to centromere heterochromatic repeats. Science 297, 1831 (2002)

    Article  CAS  Google Scholar 

  22. Schramke, V. & Allshire, R. Hairpin RNAs and retrotransposon LTRs effect RNAi and chromatin-based gene silencing. Science 301, 1069–1074 (2003)

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  24. Parrish, S., Fleenor, J., Xu, S., Mello, C. & Fire, A. Functional anatomy of a dsRNA trigger. Differential requirement for the two trigger strands in RNA interference. Mol. Cell 6, 1077–1087 (2000)

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  26. Praitis, V., Casey, E., Collar, D. & Austin, J. Creation of low-copy integrated transgenic lines in Caenorhabditis elegans. Genetics 157, 1217–1226 (2001)

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Kelly, W. G. & Fire, A. Chromatin silencing and the maintenance of a functional germline in Caenorhabditis elegans. Development 125, 2451–2456 (1998)

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Wilm, T., Demel, P., Koop, H. U., Schnabel, H. & Schnabel, R. Ballistic transformation of Caenorhabditis elegans. Gene 229, 31–35 (1999)

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  30. Fraser, A. G. et al. Functional genomic analysis of C. elegans chromosome 1 by systematic RNA interference. Nature 408, 325–330 (2000)

    Article  ADS  CAS  Google Scholar 

Download references

Acknowledgements

We thank R. Ketting for help in experiments and discussions, and E. Berezikov for help with the ballistic transformations. We acknowledge S. Fischer, N. Vastenhouw, V. Robert, E. Cuppen, R. May and M. Joosten for helpful discussions or for critically reading the manuscript. This work was supported by a VIDI fellowship from the Dutch Science Foundation (NWO) to T.S.

Author information

Authors and Affiliations

  1. Hubrecht Laboratory, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands

    Titia Sijen & Ronald H. A. Plasterk

Authors
  1. Titia Sijen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ronald H. A. Plasterk
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ronald H. A. Plasterk.

Ethics declarations

Competing interests

The authors declare that they have no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sijen, T., Plasterk, R. Transposon silencing in the Caenorhabditis elegans germ line by natural RNAi. Nature 426, 310–314 (2003). https://doi.org/10.1038/nature02107

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature02107

This article is cited by

Comments

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.

Search

Advanced 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