Integrating the genomic architecture of human nucleolar organizer regions with the biophysical properties of nucleoli

Abstract

Nucleoli are the sites of ribosome biogenesis and the largest membraneless subnuclear structures. They are intimately linked with growth and proliferation control and function as sensors of cellular stress. Nucleoli form around arrays of ribosomal gene (rDNA) repeats also called nucleolar organizer regions (NORs). In humans, NORs are located on the short arms of all five human acrocentric chromosomes. Multiple NORs contribute to the formation of large heterochromatin-surrounded nucleoli observed in most human cells. Here we will review recent findings about their genomic architecture. The dynamic nature of nucleoli began to be appreciated with the advent of photodynamic experiments using fluorescent protein fusions. We review more recent data on nucleoli in Xenopus germinal vesicles (GVs) which has revealed a liquid droplet-like behavior that facilitates nucleolar fusion. Further analysis in both Xenopus GVs and Drosophila embryos indicates that the internal organization of nucleoli is generated by a combination of liquid-liquid phase separation and active processes involving rDNA. We will attempt to integrate these recent findings with the genomic architecture of human NORs to advance our understanding of how nucleoli form and respond to stress in human cells.

New Roles for the Nucleolus in Health and Disease

“…The nucleolus is a dynamic, non‐membrane bound compartment within the nucleus, and is the hub for ribosomal RNA (rRNA) synthesis and assembly with ribosomal proteins (rproteins) to generate the ribosome subunits . The nucleolus is surrounded by the peri‐nucleolar heterochromatin (PH) and consists of three distinct structural regions defined by their appearance and the presence of specific components required for ribosome synthesis: i) the fibrillar center (FC); ii) dense fibrillar component (DFC); and iii) granular component (GC) (Figure ) …”

“…Nucleoli form around actively transcribed clusters of the 200–400 rRNA genes, which are typically arranged as tandem‐repeats, and as a consequence, occupy the same three dimensional nuclear space. In non‐transformed human cells, these genes localize to the short arms of five acrocentric chromosomes (13,14,15,21,22), forming the nucleolar organizer regions (NORs).…”

Treacle controls the nucleolar response to rDNA breaks via TOPBP1 recruitment and ATR activation

“…Pol I transcription takes place at the interface between FCs and the surrounding dense fibrillar component (DFC) where early processing of the synthesized pre-rRNA occurs. FCs and DFC are embedded in the granular component (GC) where late processing of pre-rRNAs occurs, yielding mature rRNAs that together with the ribosomal proteins assemble into ribosome subunits 15 .…”

Molecular cytogenetic characterization of small supernumerary marker 15 in infertile male: A case report

“…First, there might be an association between the nucleolar organizer region (NOR) and meiotic abnormalities. The NOR is located on the short arms of human acrocentric chromosomes and the chromosomal context of NOR has a critical role in nuclear biology (32). Additional NOR activity beyond an optimal threshold resulting from marker chromosomes may predispose to meiotic disturbances (33).…”