Involvement of human ribosomal proteins in nucleolar structure and p53-dependent nucleolar stress

• Published in: Nature communications Vol. 7; no. 1; p. 11390
• Main Authors: Nicolas, Emilien, Parisot, Pascaline, Pinto-Monteiro, Celina, de Walque, Roxane, De Vleeschouwer, Christophe, Lafontaine, Denis L. J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06.06.2016; Nature Publishing Group; Nature Portfolio
• Subjects: 14/63; 38/35; 38/39; 38/71; 38/89; 631/45/612/1249; 631/67; 631/80/386/1362; 631/80/86/2366; Biomarkers; Biosynthesis; Cancer; Cell Nucleolus - chemistry; Cell Nucleolus - genetics; Cell Nucleolus - metabolism; Humanities and Social Sciences; Humans; Microscopy; Morphology; multidisciplinary; Mutation; Proteins; Ribonucleic acid; Ribosomal Proteins - chemistry; Ribosomal Proteins - genetics; Ribosomal Proteins - metabolism; RNA; RNA polymerase; RNA, Ribosomal, 5S - chemistry; RNA, Ribosomal, 5S - metabolism; Science; Science (multidisciplinary); Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Belgium
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms11390

The nucleolus is a potent disease biomarker and a target in cancer therapy. Ribosome biogenesis is initiated in the nucleolus where most ribosomal (r-) proteins assemble onto precursor rRNAs. Here we systematically investigate how depletion of each of the 80 human r-proteins affects nucleolar structure, pre-rRNA processing, mature rRNA accumulation and p53 steady-state level. We developed an image-processing programme for qualitative and quantitative discrimination of normal from altered nucleolar morphology. Remarkably, we find that uL5 (formerly RPL11) and uL18 (RPL5) are the strongest contributors to nucleolar integrity. Together with the 5S rRNA, they form the late-assembling central protuberance on mature 60S subunits, and act as an Hdm2 trap and p53 stabilizer. Other major contributors to p53 homeostasis are also strictly late-assembling large subunit r-proteins essential to nucleolar structure. The identification of the r-proteins that specifically contribute to maintaining nucleolar structure and p53 steady-state level provides insights into fundamental aspects of cell and cancer biology. The nucleolus is a specialized functional domain of the nucleus where ribosome biogenesis is initiated and also implicated in a p53-dependent anti-tumor surveillance. Here the authors use a quantitative imaging approach to detail the role of each ribosomal protein on the structural integrity of the nucleolus and p53 homeostasis.