Nucleolar Organization and Functions in Health and Disease

Abstract

The nucleolus is a prominent, membraneless compartment found within the nucleus of eukaryotic cells. It forms around ribosomal RNA (rRNA) genes, where it coordinates the transcription, processing, and packaging of rRNA to produce ribosomal subunits. Recent efforts to characterize the biophysical properties of the nucleolus have transformed our understanding of the assembly and organization of this dynamic compartment. Indeed, soluble macromolecules condense from the nucleoplasm to form nucleoli through a process called liquid–liquid phase separation. Individual nucleolar components rapidly exchange with the nucleoplasm and separate within the nucleolus itself to form distinct subcompartments. In addition to its essential role in ribosome biogenesis, the nucleolus regulates many aspects of cell physiology, including genome organization, stress responses, senescence and lifespan. Consequently, the nucleolus is implicated in several human diseases, such as Hutchinson–Gilford progeria syndrome, Diamond–Blackfan anemia, and various forms of cancer. This Special Issue highlights new insights into the physical and molecular mechanisms that control the architecture and diverse functions of the nucleolus, and how they break down in disease.

Regulation of Functional Protein Aggregation by Multiple Factors: Implications for the Amyloidogenic Behavior of the CAP Superfamily Proteins

“…For example, HIV-1 Gag protein undergoes nucleic acid-dependent aggregation, and an excess of nucleic acids can promote the disassembly of the formed aggregates [ 86 ]. Additionally, nucleic acid-bound proteins are common components of membraneless compartments (e.g., nucleoli, germ granules, Cajal bodies, stress granules (SGs) and P-bodies) that exhibit liquid-like properties [ 17 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 ]. These cellular compartments are associated with diverse biological processes, including RNA metabolism, ribosome biogenesis, DNA damage response and signal transduction [ 87 ].…”

Recent advances in the nucleolar responses to DNA double-strand breaks

“…The nucleolus is the largest nuclear sub-structure, with an organization that is tightly linked to its role in ribosome biogenesis ( 7 , 8 ). It contains the most highly expressed genes in the cell alongside repressed heterochromatic sequences.…”

“…It contains the most highly expressed genes in the cell alongside repressed heterochromatic sequences. A high density of nucleic acids and ribosomal proteins creates a unique physical environment distinct from other cellular compartments ( 7 , 8 ). These features affect how all basic cellular functions are conducted in the nucleolus including transcription, replication and DNA repair.…”

SIRT7 Acts as a Guardian of Cellular Integrity by Controlling Nucleolar and Extra-Nucleolar Functions

“…Besides its well-characterized role in ribosomes biogenesis, the nucleolus has been recognized as a critical compartment involved in maintaining genomic stability, preventing ageing, and enabling cellular stress responses [ 37 ].…”