Abstract:
Integral nucleolar proteins such as Nucleolin and Fibrillarin play major roles in
regulating nuclear as well as nucleolar structure and function. Nucleolin interacts
with other nucleolar components such as Fibrillarin to maintain the distinct phaseseparated
morphology of the nucleolus. Interestingly, several cancers show a
significant upregulation in the levels of Nucleolin. Here, we showed that
overexpression of Nucleolin increases the sphericity of the nucleolus while nuclear
morphology remains unchanged. However, depletion of another nucleolar protein
Fibrillarin showed abnormal nuclear morphology. We also investigated the effect
Fibrillarin depletion on nuclear Lamins, as well as its effect on nucleolar morphology
and function. Fibrillarin knockdown showed an increase in the transcript levels of
Lamin A and Lamin B2. However, Fibrillarin knockdown also showed a collective
decrease in the protein levels of all nuclear lamins. We hypothesize that depletion of
Fibrillarin also decreases levels of C-MYC, which in turn associates with and
potentially downregulates transcript levels of Lamin A and Lamin B2 respectively.