Nucleolar Protein DDX18 plays a Role in Centromere and Heterochromatin Association to the Nucleolus

DDX18 is a member of the DEAD-box RNA helicases. As a nucleolar protein, DDX18 helps maintain the stemness of cells through positively regulating ribosome synthesis. Higher expression of DDX18 is associated with tumor growth from multiple tissue origins. Proximity labeling in tandem with mass spectroscopy revealed interaction between DDX18 and centromeric protein CENPA. It has been previously demonstrated that centromeres and their assembly factors cluster around nucleoli. Here we investigate the role of DDX18 at nucleoli in the context of centromere structure and function. Suppression of DDX18 through siRNA transfection led to concomitant reduction of CENPA intensity at centromeres, as well as disruption of centromeric-nucleolar association. In addition to the effects of DDX18 suppression on CENPA and the centromere, the abundance of nucleoli per nucleus was increased without obvious changes in nucleolar area or structure. Furthermore, perinucleolar heterochromatin organization was also altered in a DDX18-depleted background. Studies are underway to further investigate the role of DDX18 in CENP-A loading along with nucleolar and perinucleolar heterochromatin organization.