Fig. 7. Model for a lamin B1-nucleophosmin network maintaining nucleolar architecture. The model depicts a schematic view of nucleolar architecture and changes during transcriptional stress. Under physiological conditions (control), the active sites of rDNA synthesis are contained within fibrillarin-rich FC-DFC complexes (green beads) and surrounded by a granular component (GC) that is rich in nucleophosmin (dotted red). This component interacts with a lamin-containing filament network (blue) through an interaction between nucleophosmin and lamin B1 (blue stars). When RNA polymerase II activity is inhibited and the demand for rRNA falls, the normally highly structured active centers unfold and global nucleolar structure is disrupted. Clusters of rDNA genes that normally occupy a single FC-DFC complex are now distributed throughout the GC. Quite different structural changes are seen when RNA polymerase I activity is inhibited. When rRNA synthesis is completely switched off, the FC-DFC complexes are no longer present and fibrillarin accumulates in large peri-nucleolar aggregates. This structural change correlates with increased retention of nucleophosmin and lamin B1 in residual nucleoli, suggesting that the concentration of these components is normally regulated by the dynamic properties of nucleolar proteins. The model explains how reduced lamin B1 expression leads to loss of nucleolar structure so that fibrillarin can diffuse throughout the cell. Under these conditions, the spherical residual nucleoli seen during RNA polymerase I arrest are not seen, suggesting that this level of organization is dependent on lamin B1-nucleophosmin interactions in the GC. In the presence of NORs that position the rRNA genes, the structural framework formed by the interaction of lamin B1 with nucleophosmin would form an underlying architecture on which the localization and concentration of nucleophosmin is sufficient to drive the assembly of nucleoli as a consequence of the self-organization properties of the major nucleolar proteins. The changes seen when transcription is compromised imply that the underlying architecture is also locally dynamic. Hence, our model supports the dynamic properties of nucleolar components based on their biophysical characteristics, and explains how the nuclear localization and organization of nucleoli respond to any changing demand for RNA synthesis.