Control of Chromatin Structure by Long Noncoding RNA

Abstract

Long noncoding RNA (lncRNA) is a pivotal factor regulating various aspects of genome activity. Genome regulation via DNA methylation and post-translational histone modifications is a well-documented function of lncRNA in plants, fungi, and animals. Here, we summarize evidence showing that lncRNA also controls chromatin structure, including nucleosome positioning and chromosome looping. We focus on data from plant experimental systems, discussed in the context of other eukaryotes. We explain the mechanisms of lncRNA-controlled chromatin remodeling and the implications of the functional interplay between noncoding transcription and several different chromatin remodelers. We propose that the unique properties of RNA make it suitable for controlling chromatin modifications and structure.

Keywords: RNA Polymerase V; chromatin remodeling; chromosome looping; nucleosome.

Figure 1

Mechanisms preventing negative feedback between non-coding transcription and lncRNA-mediated nucleosome positioning. Pol V produces lncRNA, which serves as a binding scaffold for RNA-binding proteins including IDN2 (top). IDN2 recruits the SWI/SNF chromatin remodeling complex, which positions nucleosomes. Positioned nucleosomes contribute to repression of Pol II transcription. In a subsequent round of transcription (bottom) the previously positioned nucleosome could prevent Pol V from transcribing and reinforcing silencing. The RDD complex, which includes the putative chromatin remodeler DRD1, is proposed to remove the nucleosome and facilitate Pol V transcription, thereby preventing negative feedback between lncRNA and lncRNA-mediated nucleosome positioning.

Figure 2

Feedback between non-coding transcription and chromatin in TGS. lncRNA mediates repressive chromatin modifications (DNA methylation and H3K9me2), which facilitate non-coding transcription. Therefore, lncRNA-mediated repressive chromatin modifications are maintained by a positive feedback loop. lncRNA-mediated nucleosome positioning creates a physical obstacle to subsequent rounds of transcription. This way, there is negative feedback between non-coding transcription and nucleosome positioning, which could prevent efficient silencing. Additional chromatin remodelers are presumed to prevent this negative feedback and facilitate efficient silencing.

Figure 3

Proposed unique features that make lncRNA a versatile factor in controlling chromatin structure. (a) lncRNA may work in cis by staying attached to the transcribing RNA polymerase. Nascent lncRNA provides a binding site for RNA binding proteins. RNA-binding proteins interact with lncRNA by a sequence- or structure-specific mechanism. (b) lncRNA may work in trans by combining nucleotide sequence and complex three-dimensional structure. Sequence complementarity may facilitate lncRNA binding to specific loci in the genome. A complex three-dimensional structure may allow interaction with proteins that are recruited to chromatin or mediate chromosome looping.