3 years ago

Lamin B2 modulates nucleolar morphology, dynamics and function.

Sengupta, Sen Gupta
The nucleolus is required for ribosome biogenesis. Human cells have 2-3 nucleoli associated with Nucleolar Organizer Region (NOR) bearing chromosomes. Increase in number and altered nucleolar morphology define cancer cells. However, the mechanisms that modulate nucleolar morphology and function are unclear. Here we show that in addition to the nuclear envelope, Lamin B2 localizes proximal to Nucleolin at the Granular Component (GC) of the nucleolus and associates with nucleolar proteins - Nucleolin and Nucleophosmin. Lamin B2 knockdown severely disrupts nucleolar morphology, which was rescued to intact and discrete nucleoli upon Lamin B2 overexpression. Furthermore, two mutually exclusive Lamin B2 deletion mutants - ΔHead and ΔSLS rescue nuclear and nucleolar morphology defects respectively, induced upon Lamin B2 depletion, suggesting independent roles for Lamin B2 at the nucleolus and nuclear envelope. Lamin B2 depletion increases Nucleolin aggregation in the nucleoplasm, implicating Lamin B2 in stabilizing Nucleolin within the nucleolus. Lamin B2 knockdown upregulates nucleolar specific 45S rRNA and upstream intergenic transcripts (IGS). The IGS transcripts co-localized with aggregates of Nucleolin speckles, which were sustained in the nucleoplasm upon Lamin B2 depletion. Taken together, these studies uncover a novel role for Lamin B2 in modulating the morphology, dynamics and function of the nucleolus.

Publisher URL: http://doi.org/10.1128/MCB.00274-17

DOI: 10.1128/MCB.00274-17

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