The role of small non-coding RNAs in genome stability and chromatin organization

Abstract

SummarySmall non-coding RNAs make up much of the RNA content of a cell and have the potential to regulate gene expression on many different levels. Initial discoveries in the 1990s and early 21st century focused on determining mechanisms of post-transcriptional regulation mediated by small-interfering RNAs (siRNAs) and microRNAs (miRNAs). More recent research, however, has identified new classes of RNAs and new regulatory mechanisms, expanding the known regulatory potential of small non-coding RNAs to encompass chromatin regulation. In this Commentary, we provide an overview of these chromatin-related mechanisms and speculate on the extent to which they are conserved among eukaryotes.Key words: Argonaute, Chromatin, Germ cell, Methylation, piRNA, siRNA Journal of Cell Scienceby proteins that have a bromodomain and is associated with active transcription. Conversely, lysine methylation can be associated with either activation or repression of transcription, depending on the exact site of the mark. Methylation of lysine 9 of histone 3 (H3K9me) can be recognized by chromodomain proteins, such as heterochromatin protein 1 (HP1), which recruits deacetylating activity to the locus and induces packaging into inactive heterochromatin. Methylated lysine 4 of the same histone (H3K4me) can be bound by double-chromodomain proteins, such as CHD1, or by plant homeodomain (PHD) proteins, and recruits enzymatic activities that promote active, open chromatin. It is, however, important to note that the effect of a histone modification is highly dependent on its total context -it is too simplistic to regard individual modifications as being activating or repressing. In the context of small-RNA-induced chromatin modification, the H3K9 methylation has been best described. This modification is recognized by the RNA-induced transcriptional silencing (RITS) complex, as will be discussed below.Although not common to all eukaryotes, methylation of DNA itself constitutes a more stable type of modification than histone modification. Cytosines, particularly those in a CpG context, can be methylated in the DNA of plants and mammals. CpG methylation is symmetrical and found in both sister chromatids following genome duplication. Non-CpG methylation often is asymmetrical and must be readjusted after every cell division to be maintained, and is therefore less stable than symmetrical methylation. Non-CpG methylation has mainly been described in plants. Both types of DNA methylation generally induce the formation of compact, inactive chromatin, although in plants some methylation of open reading frames is associated with active transcription (for a review, see Munshi et al., 2009;Quina et al., 2006). Control of transposable elementsTransposable elements were first discovered in the 1940s (McClintock, 1950) and are now known to make up a large portion of the genomes of most organisms. For example, 10% of the Arabidopsis genome consists of transposons and transposon remains, and transposons account for 45% of the sequence of the human genome. The a...

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