Involvement of human ribosomal proteins in nucleolar structure and p53-dependent nucleolar stress.
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.
RNA Molecular Biology, F.R.S./FNRS, Université Libre de Bruxelles, B-6041 Charleroi-Gosselies, Belgium.|Center for Microscopy and Molecular Imaging, B-6041 Charleroi-Gosselies, Belgium.
Emilien
E
Nicolas
ICTEAM-ELEN, Université catholique de Louvain, B-1348 Louvain-la-Neuve, Belgium.
Pascaline
P
Parisot
RNA Molecular Biology, F.R.S./FNRS, Université Libre de Bruxelles, B-6041 Charleroi-Gosselies, Belgium.
Celina
C
Pinto-Monteiro
RNA Molecular Biology, F.R.S./FNRS, Université Libre de Bruxelles, B-6041 Charleroi-Gosselies, Belgium.
Roxane
R
de Walque
ICTEAM-ELEN, Université catholique de Louvain, B-1348 Louvain-la-Neuve, Belgium.
Christophe
C
De Vleeschouwer
RNA Molecular Biology, F.R.S./FNRS, Université Libre de Bruxelles, B-6041 Charleroi-Gosselies, Belgium.|Center for Microscopy and Molecular Imaging, B-6041 Charleroi-Gosselies, Belgium.
Denis L J
DL
Lafontaine
D002466:Cell Nucleolus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D012341:RNA, Ribosomal, 5S / Q000737:chemistry / Q000378:metabolism; D012269:Ribosomal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D012341:RNA, Ribosomal, 5S; D012269:Ribosomal Proteins; D016159:Tumor Suppressor Protein p53; C027624:ribosomal protein L11; C549166:ribosomal protein L5, human