Nuclear bodies: multifunctional companions of the genome

Abstract

It has become increasingly apparent that gene expression is regulated by the functional interplay between spatial genome organization and nuclear architecture. Within the nuclear environment a variety of distinct nuclear bodies exist. They are dynamic, self-organizing structures that do not assemble as pre-formed entities but rather emerge as a direct reflection of specific activities associated with gene expression and genome maintenance. Here I summarize recent findings on functions of some of the most prominent nuclear bodies, including the nucleolus, Cajal body, PML nuclear body, Polycomb group body and the 53BP1 nuclear body. The emerging view is that their organization is orchestrated by similar principles, and they function in fundamental cellular processes involved in homeostasis, differentiation, development and disease.

Figure 1. Nuclear bodies (NBs) facilitate more efficient interactions between substrates and enzymes

NBs act as a depot to concentrate a variety of reactive molecules or enzymes – each of which is represented as a Pac-Man in the schematic - and their cognate substrates (triangles) relative to the larger nucleoplasmic space. As a result, production of the relevant products (squares) is accelerated. The variety of enzymes, substrates and products are represented by different colors.

Figure 2. The core-helix model depicting the topology of transcribing ribosomal RNA genes within the mammalian nucleolus

(A) The key transcriptional initiation complex SL1 binds and holds together the promoter, upstream regulatory region and terminator, which establishes DNA looping between the sites of transcription initiation and termination. The SL1-core functions as the anchoring hub of the rDNA structure, with the transcribed ribosomal DNA region wrapped around it in a pattern of consecutive rows of non-intersecting DNA rings in a helix-like cylindrical manner. The pulling forces of elongating RNA polymerases I, which after initiation at the promoter in the core move to the outer rim of the helix, rotate the entire anchoring core around its axis, with nascent pre-rRNA transcripts radiating away from the ribosomal DNA helix, preventing them from intertwining. Only a subset of polymerases at the top and bottom of the coiled rDNA are shown for clarity (dashed lines). (B) Scheme of three subnucleolar compartments in frontal projection of the core-helix structure model. SL1 initiation complex is located in the centrally positioned Fibrillar center (FC). The active ribosomal genes with engaged RNA polymerases I are located at the periphery of the FC. Growing nascent pre-rRNA transcripts are cotranscriptionally assembled into processing ribonucleoprotein particles which form dense fibrillar component (DFC). Large (60S) and small (40S) pre-ribosomal subunits are assembled in the granular component (GC). The images were adapted from [11**].

Figure 3. Polycomb group (PcG) bodies act as a hub to recruit and silence multiple specific gene loci

PcG bodies contribute to gene silencing by harboring long-range interactions of PcG-target genes within these bodies by the PcG repressive complexes. Methylation of histone H3 at lysine 27 (H3K27me3) by PcG repressive complex PRC2 recruits the silencing complex PRC1 to enact chromatin condensation.