RRP12 (ribosomal RNA processing 12 homolog), a nucleolar protein, plays important roles in cell cycle progression and the response to deoxyribonucleic acid (DNA) damage in yeast cells. However, its role has not been investigated in mammalian cells that possess p53, which has close functional association to nucleolus. We explored the role of RRP12 in nucleolar stress condition using an osteosarcoma cell line, U2OS. To induce DNA damage and nucleolar disruption, two cytotoxic drugs, doxorubicin and actinomycin D were used. Cytotoxic stress resulted nucleolar disruption induced cell cycle arrest and apoptosis in U2OS cells. However, RRP12 overexpression promoted resistance to cytotoxic stress. In contrast, RRP12 silencing enhanced susceptibility to cytotoxic stress. During drug treatment, p53 activity and cell death were suppressed by RRP12 overexpression but promoted by RRP12 silencing. This study demonstrated that RRP12 was crucial for cell survival during cytotoxic stress via the repression of p53 stability. Thus, targeting RRP12 may enhance chemotherapeutic effect in cancers.
Keywords: Actinomycin D; Doxorubicin; Nucleolar stress; Ribosomal RNA processing 12 homolog.