The nucleolus as a multiphase liquid condensate.
Journal
Nature reviews. Molecular cell biology
ISSN: 1471-0080
Titre abrégé: Nat Rev Mol Cell Biol
Pays: England
ID NLM: 100962782
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
accepted:
07
07
2020
pubmed:
3
9
2020
medline:
12
3
2021
entrez:
3
9
2020
Statut:
ppublish
Résumé
The nucleolus is the most prominent nuclear body and serves a fundamentally important biological role as a site of ribonucleoprotein particle assembly, primarily dedicated to ribosome biogenesis. Despite being one of the first intracellular structures visualized historically, the biophysical rules governing its assembly and function are only starting to become clear. Recent studies have provided increasing support for the concept that the nucleolus represents a multilayered biomolecular condensate, whose formation by liquid-liquid phase separation (LLPS) facilitates the initial steps of ribosome biogenesis and other functions. Here, we review these biophysical insights in the context of the molecular and cell biology of the nucleolus. We discuss how nucleolar function is linked to its organization as a multiphase condensate and how dysregulation of this organization could provide insights into still poorly understood aspects of nucleolus-associated diseases, including cancer, ribosomopathies and neurodegeneration as well as ageing. We suggest that the LLPS model provides the starting point for a unifying quantitative framework for the assembly, structural maintenance and function of the nucleolus, with implications for gene regulation and ribonucleoprotein particle assembly throughout the nucleus. The LLPS concept is also likely useful in designing new therapeutic strategies to target nucleolar dysfunction.
Identifiants
pubmed: 32873929
doi: 10.1038/s41580-020-0272-6
pii: 10.1038/s41580-020-0272-6
doi:
Substances chimiques
Ribonucleoproteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
165-182Subventions
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA040601
Pays : United States
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