The nucleolus as a multiphase liquid condensate

Area of Science:

• Cell Biology
• Biophysics
• Molecular Biology

Background:

• The nucleolus is a prominent nuclear body crucial for ribosome biogenesis.
• Its biophysical principles of assembly and function are increasingly understood.
• Recent evidence supports the nucleolus as a multilayered biomolecular condensate formed by liquid-liquid phase separation (LLPS).

Purpose of the Study:

• To review biophysical insights into nucleolar organization and function.
• To connect nucleolar condensate structure to ribosome biogenesis and other cellular processes.
• To explore the implications of nucleolar dysfunction in diseases and aging.

Main Methods:

• Review of recent biophysical studies on nucleolar assembly and function.
• Integration of molecular and cell biology perspectives on the nucleolus.
• Analysis of the liquid-liquid phase separation (LLPS) model for nucleolar organization.

Main Results:

• The nucleolus functions as a multiphase biomolecular condensate driven by LLPS.
• LLPS facilitates ribosome biogenesis and other nucleolar functions.
• Dysregulation of nucleolar condensate organization is linked to diseases like cancer, ribosomopathies, neurodegeneration, and aging.

Conclusions:

• The LLPS model provides a quantitative framework for nucleolar assembly, structure, and function.
• Understanding nucleolar LLPS has implications for gene regulation and ribonucleoprotein particle assembly.
• The LLPS concept can guide the development of therapies for nucleolar dysfunction.