Granular component sub-phases direct ribosome biogenesis in the nucleolus

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• The nucleolus is crucial for ribosome biogenesis, with its granular component (GC) housing ribonucleoprotein particles for ribosomal subunit assembly.
• The spatial heterogeneity within the GC and its role in assembly are not well understood.

Purpose of the Study:

• To investigate the molecular basis of GC spatial heterogeneity.
• To elucidate the mechanism by which GC structure facilitates ribosome subunit assembly.

Main Methods:

• Super-resolution microscopy to visualize biomolecule localization within the GC.
• In vitro reconstitution assays to model GC condensate formation and dynamics.

Main Results:

• Key GC biomolecules (nucleophosmin/NPM1, surfeit locus protein 6/SURF6, ribosomal RNA/rRNA) exhibit heterogeneous localization within GC sub-phases.
• GC biomolecules form distinct multiphase condensates with a SURF6/rRNA core and an NPM1 shell.
• SURF6's interaction with rRNA is modulated during subunit assembly, allowing NPM1 to extract subunits, suggesting an assembly-line mechanism.

Conclusions:

• The heterogeneous structure of the GC arises from distinct biomolecular condensates.
• These sub-phases facilitate ribosome subunit assembly through a dynamic, assembly-line-like process.