Role of Nucleolar Factors in Modulating Nuclear Architecture

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.