DDX18 Influences Nucleolar Structure, Centromere Association, and Centromere Deposition through HJURP
Session Number
1
Advisor(s)
Dr. Sui Huang, Northwestern University
Location
A123
Discipline
Medical and Health Sciences
Start Date
15-4-2026 10:15 AM
End Date
15-4-2026 11:00 AM
Abstract
DDX18 is a DEAD-box RNA helicase primarily known for its role in maintaining the stemness of cells by positively regulating ribosome synthesis. Furthermore, higher expression of DDX18 is positively associated with tumor growth in multiple tissue origins. Proximity labeling in tandem with mass spectroscopy revealed interactions 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 nucleolar structure, centromere association, and its relation to the CENPA deposition pathway. Suppression of DDX18 by siRNA transfection led to a reduction in CENPA intensity and disruption of centromeric-nucleolar association. There was also a significant increase in nucleoli abundance in knockdown cells, highlighting DDX18’s role in nucleolar structure. Furthermore, HJURP expression was significantly reduced in siDDX18-treated cells. This reduction suggests that DDX18 may affect centromere deposition via HJURP, with prior internal experiments indicating no association between DDX18 and the upstream Mis18 complex. Continuing investigation of the centromere deposition pathway and its association with nucleoli would provide deeper insights into the multi-step processes by which cancer cells evade proliferation controls, immune system surveillance, and bypass apoptosis- ultimately leading to metastasis and mortality.
DDX18 Influences Nucleolar Structure, Centromere Association, and Centromere Deposition through HJURP
A123
DDX18 is a DEAD-box RNA helicase primarily known for its role in maintaining the stemness of cells by positively regulating ribosome synthesis. Furthermore, higher expression of DDX18 is positively associated with tumor growth in multiple tissue origins. Proximity labeling in tandem with mass spectroscopy revealed interactions 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 nucleolar structure, centromere association, and its relation to the CENPA deposition pathway. Suppression of DDX18 by siRNA transfection led to a reduction in CENPA intensity and disruption of centromeric-nucleolar association. There was also a significant increase in nucleoli abundance in knockdown cells, highlighting DDX18’s role in nucleolar structure. Furthermore, HJURP expression was significantly reduced in siDDX18-treated cells. This reduction suggests that DDX18 may affect centromere deposition via HJURP, with prior internal experiments indicating no association between DDX18 and the upstream Mis18 complex. Continuing investigation of the centromere deposition pathway and its association with nucleoli would provide deeper insights into the multi-step processes by which cancer cells evade proliferation controls, immune system surveillance, and bypass apoptosis- ultimately leading to metastasis and mortality.