Granular component sub-phases direct ribosome biogenesis in the nucleolus

Le résumé fourni par la source

The hierarchical, multiphase organization of the nucleolus underlies ribosome biogenesis. Ribonucleoprotein particles that regulate ribosomal subunit assembly are heterogeneously distributed in the nucleolar granular component (GC). However, the molecular origins of the GC's spatial heterogeneity and their link to ribosome subunit assembly remain poorly understood. Here, using super-resolution microscopy in DLD-1 cells, we uncover that key GC biomolecules-NPM1, SURF6, and ribosomal RNA (rRNA)-are heterogeneously localized within GC sub-phases. In vitro reconstitution with E. coli- and human-derived rRNA revealed that these GC biomolecules form multiphase condensates with a SURF6/rRNA-rich core and NPM1-rich shell, providing a mechanistic basis for this heterogeneity. SURF6's association with rRNA weakens upon ribosome subunit assembly, enabling NPM1 to extract assembled subunits from condensates, suggesting an assembly-line-like mechanism of subunit efflux from the GC. Our results establish a framework for understanding the GC's heterogeneous structure and reveal how its distinct sub-phases facilitate ribosome subunit assembly.

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