Mechanisms of Gene Silencing

Gene silencing can be broadly attributed to processes that occur at the transcrip-tional (transcriptional gene silencing, TGS) or post-transcriptional level (post-transcriptional gene silencing, PTGS; now also referred to as RNA silencing).

Down-regulation of gene expression by TGS:

  1. Involves inhibition of primary transcription by epigenetic mechanisms and generally correlates with DNA methylation of the promoter and chromatin condensation (heterochromatinization),
  2. Is frequently induced and/or maintained by small RNA-mediated processes including RNA-directed DNA methylation and RNA-directed chromatin condensation,
  3. Is not graft-transmissible, which was suggested to be due to the nuclear com-partmentalization of TGS (Mourrain et al. 2007),
  4. Is mitotically and meiotically heritable but may also be reversed, a process that is accompanied by loss of DNA methylation, can occur gradually over several generations, and is often observed when the initial trigger of silencing is removed.

Down-regulation of gene expression by PTGS:

  1. Acts on mRNA in the cytoplasm and generally results in transcript degradation,
  2. Is a sequence-specific process that is mediated by small RNA molecules,
  3. Can spread systemically and is graft-transmissible,
  4. Is meiotically not heritable in the absence of the initial trigger but in some cases may be maintained throughout the lifespan of a plant even when the trigger of silencing is removed,
  5. Can involve RNA-directed DNA methylation of the transcribed region of a gene.

TGS and PTGS can also be distinguished by distinct enzymatic machineries and inhibitors, although some proteins appear to be involved in both processes.

While the terms TGS and PTGS have often been used to categorize silencing events, it is now well established that these processes are strongly interrelated and exert mutual effects on one another, and it has been suggested that both derive from a common ancestral mechanism (for recent reviews on RNA silencing and regulatory crosstalks between transcriptional and post-transcriptional processes in plants, see Grant-Downton and Dickinson 2005; Brodersen and Voinnet 2006; Henderson and Jacobsen 2007; Huettel et al. 2007; Eamens et al. 2008a; Hollick 2008; Pikaard et al. 2008). In particular, small RNA molecules that are an essential intermediate of PTGS are also effectors of DNA methylation and TGS, and -conversely - transcription of methylated templates is required for the maintenance of PTGS (Eamens et al. 2008b and references therein). The following section will therefore briefly review the production and significance of small RNAs as intermediates of gene-silencing pathways.

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