The nucleolus as a multiphase liquid condensate

Abstract

Among numerous microscopically visible nuclear substructures, the nucleolus is the most prominent and represents a functionally and biophysically distinct body or compartment. The nucleolus is, in fact, so prominent that it drew the attention of early biologists over 200 years ago, in light microscopy studies by Fontana, Valentin and Wagner 1. Following these early descriptions came the understanding of the functional importance of the nucleolus, including its primary role as the site for the initial steps of ribosome biogenesis, including RNA polymerase I (Pol I)-driven transcription, processing and modification of ribosomal RNA (rRNA) and the assembly of rRNA-containing complexes 2 (Fig. 1). These processes involve several hundred protein transacting factors and small nucleolar RNAs 3 , which serve to guide the specificity of rRNA chemical modifications, pre-rRNA folding and cleavage. Once precursor subunits are released from the nucleolar structure, they undergo further maturation in the nucleoplasm and cytoplasm prior to becoming fully functional ribosomal subunits, ready to engage in translating mRNA into protein. This nucleolar function is accompanied by organization of the nucleolus into distinct subcompartments. In mammalian cells, nucleoli display three layers, nested like Russian dolls, where successive steps of ribosome production take place, starting

Properties and biological impact of RNA G-quadruplexes: from order to turmoil and back

“…Gelation is related to liquid–liquid phase separation (LLPS), a fundamental physical phenomenon describing a density transition of an initially homogenous solution into a dense and a dilute liquid phase that can stably coexist. This phenomenon underlies many biological processes including the formation of membraneless compartments (reviewed in ( 183 )), notably RNA-containing subcellular entities (called RNA granules) such as the nucleolus in the nucleus ( 184 ) and SGs in the cytoplasm ( 181 ).…”

Repulsive electrostatic interactions modulate dense and dilute phase properties of biomolecular condensates

“…Some of these biomolecular condensates are constitutive in eukaryotic cells (1), while others only occur in specific cell types or in response to certain environmental stimuli (2–8). While a condensate may contain hundreds of different components (4), its composition is typically dominated by a small number of major constituents that define the condensate identity and likely control its overall biochemical and biophysical properties (1, 2, 5, 9). These high abundance constituents can be thought of as the basis of the condensate’s unique internal solvent environment, into which other (solute) biomolecules may be partitioned.…”

Surface condensation of a pioneer transcription factor on DNA

“…In the last decade, extensive studies on the properties of non-membrane-bound compartments in the cellular cytoplasm have shown that concepts in phase separation drawn from physical chemistry can describe their formation and behaviour [1][2][3][4] . Current evidence also suggests that phase separation plays a role in the organization inside the cell nucleus [5][6][7][8] . However, the influence and role of DNA on the physical chemistry of phase separation is not well understood.…”