Nothing Special   »   [go: up one dir, main page]
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 RNAs in transcriptional gene silencing and genome defence

Nature volume 457, pages 413–420 (2009)Cite this article

Abstract

Small RNA molecules of about 20–30 nucleotides have emerged as powerful regulators of gene expression and genome stability. Studies in fission yeast and multicellular organisms suggest that effector complexes, directed by small RNAs, target nascent chromatin-bound non-coding RNAs and recruit chromatin-modifying complexes. Interactions between small RNAs and nascent non-coding transcripts thus reveal a new mechanism for targeting chromatin-modifying complexes to specific chromosome regions and suggest possibilities for how the resultant chromatin states may be inherited during the process of chromosome duplication.

Access through your institution
Buy or subscribe

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

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

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

Figure 1: Pathways of RNA processing and biogenesis of small RNAs.
Figure 2: Chromosome organization and the nascent transcript model for heterochromatic gene-silencing assembly in Schizosaccharomyces pombe.
Figure 3: Argonaute complexes that link RNA silencing to chromatin modifications.

Similar content being viewed by others

References

  1. 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 

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

    ADS  CAS  PubMed  Google Scholar 

  3. Buhler, M. & Moazed, D. Transcription and RNAi in heterochromatic gene silencing. Nature Struct. Mol. Biol. 14, 1041–1048 (2007).

    Google Scholar 

  4. Aravin, A. A., Hannon, G. J. & Brennecke, J. The Piwi–piRNA pathway provides an adaptive defense in the transposon arms race. Science 318, 761–764 (2007).

    ADS  CAS  PubMed  Google Scholar 

  5. 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 

  6. 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 

  7. 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 

  8. 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 

  9. 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). This study describes the biochemical isolation of RISC.

    ADS  CAS  PubMed  Google Scholar 

  10. Verdel, A. et al. RNAi-mediated targeting of heterochromatin by the RITS complex. Science 303, 672–676 (2004). This study describes the purification and component identification of RITS, which physically links RNAi to heterochromatin.

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  11. Carmell, M. A., Xuan, Z., Zhang, M. Q. & Hannon, G. J. The Argonaute family: tentacles that reach into RNAi, developmental control, stem cell maintenance, and tumorigenesis. Genes Dev. 16, 2733–2742 (2002).

    CAS  PubMed  Google Scholar 

  12. Aravin, A. et al. A novel class of small RNAs bind to MILI protein in mouse testes. Nature 442, 203–207 (2006).

    ADS  CAS  PubMed  Google Scholar 

  13. Girard, A., Sachidanandam, R., Hannon, G. J. & Carmell, M. A. A germline-specific class of small RNAs binds mammalian Piwi proteins. Nature 442, 199–202 (2006).

    ADS  PubMed  Google Scholar 

  14. Grivna, S. T., Beyret, E., Wang, Z. & Lin, H. A novel class of small RNAs in mouse spermatogenic cells. Genes Dev. 20, 1709–1714 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Lau, N. C. et al. Characterization of the piRNA complex from rat testes. Science 313, 363–367 (2006).

    ADS  CAS  PubMed  Google Scholar 

  16. Watanabe, T. et al. Identification and characterization of two novel classes of small RNAs in the mouse germline: retrotransposon-derived siRNAs in oocytes and germline small RNAs in testes. Genes Dev. 20, 1732–1743 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Batista, P. J. et al. PRG-1 and 21U-RNAs interact to form the piRNA complex required for fertility in C. elegans . Mol. Cell 31, 67–78 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Das, P. P. et al. Piwi and piRNAs act upstream of an endogenous siRNA pathway to suppress Tc3 transposon mobility in the Caenorhabditis elegans germline. Mol. Cell 31, 79–90 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Filipowicz, W., Jaskiewicz, L., Kolb, F. A. & Pillai, R. S. Post-transcriptional gene silencing by siRNAs and miRNAs. Curr. Opin. Struct. Biol. 15, 331–341 (2005).

    CAS  PubMed  Google Scholar 

  20. Bao, N., Lye, K. W. & Barton, M. K. MicroRNA binding sites in Arabidopsis class III HD-ZIP mRNAs are required for methylation of the template chromosome. Dev. Cell 7, 653–662 (2004).

    CAS  PubMed  Google Scholar 

  21. Gonzalez, S., Pisano, D. G. & Serrano, M. Mechanistic principles of chromatin remodeling guided by siRNAs and miRNAs. Cell Cycle 7, 2601–2608 (2008).

    CAS  PubMed  Google Scholar 

  22. Kim, D. H., Saetrom, P., Snove, O. Jr & Rossi, J. J. MicroRNA-directed transcriptional gene silencing in mammalian cells. Proc. Natl Acad. Sci. USA 105, 16230–16235 (2008).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ghildiyal, M. et al. Endogenous siRNAs derived from transposons and mRNAs in Drosophila somatic cells. Science 320, 1077–1081 (2008).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  24. Chung, W. J., Okamura, K., Martin, R. & Lai, E. C. Endogenous RNA interference provides a somatic defense against Drosophila transposons. Curr. Biol. 18, 795–802 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Kawamura, Y. et al. Drosophila endogenous small RNAs bind to Argonaute 2 in somatic cells. Nature 453, 793–797 (2008).

    ADS  CAS  PubMed  Google Scholar 

  26. 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  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  28. Buhler, M., Haas, W., Gygi, S. P. & Moazed, D. RNAi-dependent and -independent RNA turnover mechanisms contribute to heterochromatic gene silencing. Cell 129, 707–721 (2007). This study identified a role for co-transcriptional RNA processing, mediated by the TRAMP/exosome pathway, as an additional layer of regulation that is required for efficient heterochromatic gene silencing.

    CAS  PubMed  Google Scholar 

  29. Buhler, M., Spies, N., Bartel, D. P. & Moazed, D. TRAMP-mediated RNA surveillance prevents spurious entry of RNAs into the Schizosaccharomyces pombe siRNA pathway. Nature Struct. Mol. Biol. 15, 1015–1023 (2008).

    Google Scholar 

  30. Wyers, F. et al. Cryptic Pol II transcripts are degraded by a nuclear quality control pathway involving a new poly(A) polymerase. Cell 121, 725–737 (2005).

    CAS  PubMed  Google Scholar 

  31. LaCava, J. et al. RNA degradation by the exosome is promoted by a nuclear polyadenylation complex. Cell 121, 713–724 (2005).

    CAS  PubMed  Google Scholar 

  32. Wassenegger, M., Heimes, S., Riedel, L. & Sanger, H. L. RNA-directed de novo methylation of genomic sequences in plants. Cell 76, 567–576 (1994).

    CAS  PubMed  Google Scholar 

  33. Mette, M. F., Aufsatz, W., van der Winden, J., Matzke, M. A. & Matzke, A. J. Transcriptional silencing and promoter methylation triggered by double-stranded RNA. EMBO J. 19, 5194–5201 (2000). These two studies described a role for RNA in promoting the methylation of homologous genomic sequences in plants.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Zilberman, D., Cao, X. & Jacobsen, S. E. ARGONAUTE4 control of locus-specific siRNA accumulation and DNA and histone methylation. Science 299, 716–719 (2003).

    ADS  CAS  PubMed  Google Scholar 

  35. Henderson, I. R. et al. Dissecting Arabidopsis thaliana DICER function in small RNA processing, gene silencing and DNA methylation patterning. Nature Genet. 38, 721–725 (2006).

    CAS  PubMed  Google Scholar 

  36. Lippman, Z., May, B., Yordan, C., Singer, T. & Martienssen, R. Distinct mechanisms determine transposon inheritance and methylation via small interfering RNA and histone modification. PLoS Biol. 1, e67 (2003).

    PubMed  PubMed Central  Google Scholar 

  37. Volpe, T. A. et al. Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science 297, 1833–1837 (2002). This study identified a role for components of the RNAi pathway in heterochromatin assembly and gene silencing at S. pombe centromeres.

    ADS  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  39. Cam, H. P. et al. Comprehensive analysis of heterochromatin- and RNAi-mediated epigenetic control of the fission yeast genome. Nature Genet. 37, 809–819 (2005).

    CAS  PubMed  Google Scholar 

  40. Mochizuki, K., Fine, N. A., Fujisawa, T. & Gorovsky, M. A. Analysis of a piwi-related gene implicates small RNAs in genome rearrangement in Tetrahymena . Cell 110, 689–699 (2002). This study identified a role for T. thermophila TWI1, a PIWI-clade Argonaute protein, and small RNAs in mediating DNA elimination.

    CAS  PubMed  Google Scholar 

  41. Taverna, S. D., Coyne, R. S. & Allis, C. D. Methylation of histone H3 at lysine 9 targets programmed DNA elimination in Tetrahymena . Cell 110, 701–711 (2002).

    CAS  PubMed  Google Scholar 

  42. Liu, Y. et al. RNAi-dependent H3K27 methylation is required for heterochromatin formation and DNA elimination in Tetrahymena . Genes Dev. 21, 1530–1545 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Pal-Bhadra, M. et al. Heterochromatic silencing and HP1 localization in Drosophila are dependent on the RNAi machinery. Science 303, 669–672 (2004).

    ADS  CAS  PubMed  Google Scholar 

  44. Ringrose, L. & Paro, R. Epigenetic regulation of cellular memory by the Polycomb and Trithorax group proteins. Annu. Rev. Genet. 38, 413–443 (2004).

    CAS  PubMed  Google Scholar 

  45. Deshpande, G., Calhoun, G. & Schedl, P. Drosophila argonaute-2 is required early in embryogenesis for the assembly of centric/centromeric heterochromatin, nuclear division, nuclear migration, and germ-cell formation. Genes Dev. 19, 1680–1685 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Haynes, K. A., Caudy, A. A., Collins, L. & Elgin, S. C. Element 1360 and RNAi components contribute to HP1-dependent silencing of a pericentric reporter. Curr. Biol. 16, 2222–2227 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Grishok, A., Sinskey, J. L. & Sharp, P. A. Transcriptional silencing of a transgene by RNAi in the soma of C. elegans . Genes Dev. 19, 683–696 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Robert, V. J., Sijen, T., van Wolfswinkel, J. & Plasterk, R. H. Chromatin and RNAi factors protect the C. elegans germline against repetitive sequences. Genes Dev. 19, 782–787 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Kim, J. K. et al. Functional genomic analysis of RNA interference in C. elegans . Science 308, 1164–1167 (2005).

    ADS  CAS  PubMed  Google Scholar 

  50. Grimaud, C. et al. RNAi components are required for nuclear clustering of Polycomb group response elements. Cell 124, 957–971 (2006).

    CAS  PubMed  Google Scholar 

  51. Grewal, S. I. & Elgin, S. C. Transcription and RNA interference in the formation of heterochromatin. Nature 447, 399–406 (2007).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  52. Folco, H. D., Pidoux, A. L., Urano, T. & Allshire, R. C. Heterochromatin and RNAi are required to establish CENP-A chromatin at centromeres. Science 319, 94–97 (2008).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  53. Zaratiegui, M., Irvine, D. V. & Martienssen, R. A. Noncoding RNAs and gene silencing. Cell 128, 763–776 (2007).

    CAS  PubMed  Google Scholar 

  54. Grewal, S. I. & Jia, S. Heterochromatin revisited. Nature Rev. Genet. 8, 35–46 (2007).

    CAS  PubMed  Google Scholar 

  55. Rea, S. et al. Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature 406, 593–599 (2000).

    ADS  CAS  PubMed  Google Scholar 

  56. Lachner, M., O'Carroll, D., Rea, S., Mechtler, K. & Jenuwein, T. Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410, 116–120 (2001).

    ADS  CAS  PubMed  Google Scholar 

  57. Bannister, A. J. et al. Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature 410, 120–124 (2001).

    ADS  CAS  PubMed  Google Scholar 

  58. Nakayama, J., Rice, J. C., Strahl, B. D., Allis, C. D. & Grewal, S. I. Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly. Science 292, 110–113 (2001).

    ADS  CAS  PubMed  Google Scholar 

  59. Partridge, J. F., Borgstrom, B. & Allshire, R. C. Distinct protein interaction domains and protein spreading in a complex centromere. Genes Dev. 14, 783–791 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Sadaie, M., Iida, T., Urano, T. & Nakayama, J. A chromodomain protein, Chp1, is required for the establishment of heterochromatin in fission yeast. EMBO J. 23, 3825–3835 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Motamedi, M. R. et al. Two RNAi complexes, RITS and RDRC, physically interact and localize to noncoding centromeric RNAs. Cell 119, 789–802 (2004).

    CAS  PubMed  Google Scholar 

  62. Sugiyama, T., Cam, H., Verdel, A., Moazed, D. & Grewal, S. I. RNA-dependent RNA polymerase is an essential component of a self-enforcing loop coupling heterochromatin assembly to siRNA production. Proc. Natl Acad. Sci. USA 102, 152–157 (2005). These two studies identified the S. pombe RdRP complex and demonstrated that it has in vitro dsRNA synthesis activity and is associated with RITS and non-coding centromeric RNA. They further showed that the dsRNA synthesis activity is required for RNAi-mediated gene silencing.

    ADS  CAS  PubMed  Google Scholar 

  63. Buker, S. M. et al. Two different Argonaute complexes are required for siRNA generation and heterochromatin assembly in fission yeast. Nature Struct. Mol. Biol. 14, 200–207 (2007).

    CAS  Google Scholar 

  64. Irvine, D. V. et al. Argonaute slicing is required for heterochromatic silencing and spreading. Science 313, 1134–1137 (2006).

    ADS  CAS  PubMed  Google Scholar 

  65. Noma, K. et al. RITS acts in cis to promote RNA interference-mediated transcriptional and post-transcriptional silencing. Nature Genet. 36, 1174–1180 (2004).

    CAS  PubMed  Google Scholar 

  66. Buhler, M., Verdel, A. & Moazed, D. Tethering RITS to a nascent transcript initiates RNAi- and heterochromatin-dependent gene silencing. Cell 125, 873–886 (2006). This study demonstrated that tethering of the Tas3 component of RITS to the RNA transcript of a euchromatic reporter gene induced RNAi and heterochromatin assembly at the reporter gene.

    CAS  PubMed  Google Scholar 

  67. Hong, E.-J. E., Villen, J., Gerace, E. L., Gygi, S. P. & Moazed, D. A Cullin E3 ubiquitin ligase complex associates with Rik1 and the Clr4 histone H3-K9 methyltransferase and is required for RNAi-mediated heterochromatin formation. RNA Biol. 2, 106–111 (2005).

    CAS  PubMed  Google Scholar 

  68. Bayne, E. H. et al. Splicing factors facilitate RNAi-directed silencing in fission yeast. Science 322, 602–606 (2008).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  69. Wutz, A. RNAs templating chromatin structure for dosage compensation in animals. Bioessays 25, 434–442 (2003).

    CAS  PubMed  Google Scholar 

  70. Iida, T., Nakayama, J. & Moazed, D. siRNA-mediated heterochromatin establishment requires HP1 and is associated with antisense transcription. Mol. Cell 31, 178–189 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Motamedi, M. R. et al. HP1 proteins form distinct complexes and mediate heterochromatic gene silencing by non-overlapping mechanisms. Mol. Cell 32, 778–790 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Colmenares, S. U., Buker, S. M., Buhler, M., Dlakic, M. & Moazed, D. Coupling of double-stranded RNA synthesis and siRNA generation in fission yeast RNAi. Mol. Cell 27, 449–461 (2007).

    CAS  PubMed  Google Scholar 

  73. Sarot, E., Payen-Groschene, G., Bucheton, A. & Pelisson, A. Evidence for a piwi-dependent RNA silencing of the gypsy endogenous retrovirus by the Drosophila melanogaster flamenco gene. Genetics 166, 1313–1321 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Reiss, D., Josse, T., Anxolabehere, D. & Ronsseray, S. aubergine mutations in Drosophila melanogaster impair P cytotype determination by telomeric P elements inserted in heterochromatin. Mol. Genet. Genomics 272, 336–343 (2004).

    CAS  PubMed  Google Scholar 

  75. Chan, S. W., Zhang, X., Bernatavichute, Y. V. & Jacobsen, S. E. Two-step recruitment of RNA-directed DNA methylation to tandem repeats. PLoS Biol. 4, e363 (2006).

    PubMed  PubMed Central  Google Scholar 

  76. Ting, A. H., Schuebel, K. E., Herman, J. G. & Baylin, S. B. Short double-stranded RNA induces transcriptional gene silencing in human cancer cells in the absence of DNA methylation. Nature Genet. 37, 906–910 (2005).

    CAS  PubMed  Google Scholar 

  77. Janowski, B. A. et al. Involvement of AGO1 and AGO2 in mammalian transcriptional silencing. Nature Struct. Mol. Biol. 13, 787–792 (2006).

    CAS  Google Scholar 

  78. Sogo, J. M., Stahl, H., Koller, T. & Knippers, R. Structure of replicating simian virus 40 minichromosomes. The replication fork, core histone segregation and terminal structures. J. Mol. Biol. 189, 189–204 (1986).

    CAS  PubMed  Google Scholar 

  79. Jenuwein, T. & Allis, C. D. Translating the histone code. Science 293, 1074–1080 (2001).

    CAS  PubMed  Google Scholar 

  80. Mello, C. C. & Conte, D. Jr. Revealing the world of RNA interference. Nature 431, 338–342 (2004).

    ADS  CAS  PubMed  Google Scholar 

  81. Zhang, K., Mosch, K., Fischle, W. & Grewal, S. I. Roles of the Clr4 methyltransferase complex in nucleation, spreading and maintenance of heterochromatin. Nature Struct. Mol. Biol. 15, 381–388 (2008).

    CAS  Google Scholar 

  82. Chen, E. S. et al. Cell cycle control of centromeric repeat transcription and heterochromatin assembly. Nature 451, 734–737 (2008).

    ADS  CAS  PubMed  Google Scholar 

  83. Vanacova, S. et al. A new yeast poly(A) polymerase complex involved in RNA quality control. PLoS Biol. 3, e189 (2005).

    PubMed  Google Scholar 

  84. Chen, C. C. et al. A member of the polymerase β nucleotidyltransferase superfamily is required for RNA interference in C. elegans . Curr. Biol. 15, 378–383 (2005).

    CAS  PubMed  Google Scholar 

  85. Lee, S. R. & Collins, K. Physical and functional coupling of RNA-dependent RNA polymerase and Dicer in the biogenesis of endogenous siRNAs. Nature Struct. Mol. Biol. 14, 604–610 (2007).

    CAS  Google Scholar 

  86. Kloc, A., Zaratiegui, M., Nora, E. & Martienssen, R. RNA interference guides histone modification during the S phase of chromosomal replication. Curr. Biol. 18, 490–495 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Kato, H. et al. RNA polymerase II is required for RNAi-dependent heterochromatin assembly. Science 309, 467–469 (2005).

    ADS  CAS  PubMed  Google Scholar 

  88. Djupedal, I. et al. RNA Pol II subunit Rpb7 promotes centromeric transcription and RNAi-directed chromatin silencing. Genes Dev. 19, 2301–2306 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. El-Shami, M. et al. Reiterated WG/GW motifs form functionally and evolutionarily conserved ARGONAUTE-binding platforms in RNAi-related components. Genes Dev. 21, 2539–2544 (2007). This study, together with references 93, 94, 95 , establishes GW-motif-containing proteins as conserved Argonaute adaptors.

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Morris, K. V., Chan, S. W., Jacobsen, S. E. & Looney, D. J. Small interfering RNA-induced transcriptional gene silencing in human cells. Science 305, 1289–1292 (2004).

    ADS  CAS  PubMed  Google Scholar 

  91. Kim, D. H., Villeneuve, L. M., Morris, K. V. & Rossi, J. J. Argonaute-1 directs siRNA-mediated transcriptional gene silencing in human cells. Nature Struct. Mol. Biol. 13, 793–797 (2006).

    CAS  Google Scholar 

  92. Carmell, M. A. et al. MIWI2 is essential for spermatogenesis and repression of transposons in the mouse male germline. Dev. Cell 12, 503–514 (2007).

    CAS  PubMed  Google Scholar 

  93. Eulalio, A., Huntzinger, E. & Izaurralde, E. GW182 interaction with Argonaute is essential for miRNA-mediated translational repression and mRNA decay. Nature Struct. Mol. Biol. 15, 346–353 (2008).

    CAS  Google Scholar 

  94. Debeauchamp, J. L. et al. Chp1–Tas3 interaction is required to recruit RITS to fission yeast centromeres and for maintenance of centromeric heterochromatin. Mol. Cell. Biol. 28, 2154–2166 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Till, S. et al. A conserved motif in Argonaute-interacting proteins mediates functional interactions through the Argonaute PIWI domain. Nature Struct. Mol. Biol. 14, 897–903 (2007).

    CAS  Google Scholar 

  96. Li, C. F. et al. An ARGONAUTE4-containing nuclear processing center colocalized with Cajal bodies in Arabidopsis thaliana . Cell 126, 93–106 (2006).

    CAS  PubMed  Google Scholar 

  97. Pontes, O. et al. The Arabidopsis chromatin-modifying nuclear siRNA pathway involves a nucleolar RNA processing center. Cell 126, 79–92 (2006).

    CAS  PubMed  Google Scholar 

  98. Kanno, T. et al. Atypical RNA polymerase subunits required for RNA-directed DNA methylation. Nature Genet. 37, 761–765 (2005).

    CAS  PubMed  Google Scholar 

  99. Herr, A. J., Jensen, M. B., Dalmay, T. & Baulcombe, D. C. RNA polymerase IV directs silencing of endogenous DNA. Science 308, 118–120 (2005).

    ADS  CAS  PubMed  Google Scholar 

  100. Brower-Toland, B. et al. Drosophila PIWI associates with chromatin and interacts directly with HP1a. Genes Dev. 21, 2300–2311 (2007). This study identifies a physical association between HP1 and PIWI, suggesting that HP1 may collaborate with PIWI in establishing repressive chromatin domains.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

I thank the members of my laboratory and colleagues in the chromatin and RNA silencing fields for fruitful discussions, and the National Institutes of Health, the Leukemia and Lymphoma Society, and the Howard Hughes Medical Institute for funding.

Author information

Authors and Affiliations

  1. and Department of Cell Biology, Howard Hughes Medical Institute, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Danesh Moazed

Authors
  1. Danesh Moazed
    View author publications

    You can also search for this author in PubMed Google Scholar

Ethics declarations

Competing interests

The author declares no competing financial interests.

Additional information

Reprints and permissions information is available at http://www.nature.com/reprints.

Correspondence should be addressed to the author(danesh_moazed@hms.harvard.edu).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Moazed, D. Small RNAs in transcriptional gene silencing and genome defence. Nature 457, 413–420 (2009). https://doi.org/10.1038/nature07756

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature07756

This article is cited by

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