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

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  • Emilien Nicolas

    (RNA Molecular Biology, F.R.S./FNRS, Université Libre de Bruxelles
    Center for Microscopy and Molecular Imaging)

  • Pascaline Parisot

    (ICTEAM-ELEN, Université catholique de Louvain)

  • Celina Pinto-Monteiro

    (RNA Molecular Biology, F.R.S./FNRS, Université Libre de Bruxelles)

  • Roxane de Walque

    (RNA Molecular Biology, F.R.S./FNRS, Université Libre de Bruxelles)

  • Christophe De Vleeschouwer

    (ICTEAM-ELEN, Université catholique de Louvain)

  • Denis L. J. Lafontaine

    (RNA Molecular Biology, F.R.S./FNRS, Université Libre de Bruxelles
    Center for Microscopy and Molecular Imaging)

Abstract

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.

Suggested Citation

  • Emilien Nicolas & Pascaline Parisot & Celina Pinto-Monteiro & Roxane de Walque & Christophe De Vleeschouwer & Denis L. J. Lafontaine, 2016. "Involvement of human ribosomal proteins in nucleolar structure and p53-dependent nucleolar stress," Nature Communications, Nature, vol. 7(1), pages 1-12, September.
  • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11390
    DOI: 10.1038/ncomms11390
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    Cited by:

    1. Melvin Pan & Christiane Zorbas & Maki Sugaya & Kensuke Ishiguro & Miki Kato & Miyuki Nishida & Hai-Feng Zhang & Marco M. Candeias & Akimitsu Okamoto & Takamasa Ishikawa & Tomoyoshi Soga & Hiroyuki Abu, 2022. "Glutamine deficiency in solid tumor cells confers resistance to ribosomal RNA synthesis inhibitors," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Samim Sharifi & Prerana Chaudhari & Asya Martirosyan & Alexander Otto Eberhardt & Finja Witt & André Gollowitzer & Lisa Lange & Yvonne Woitzat & Eberechukwu Maryann Okoli & Huahui Li & Norman Rahnis &, 2024. "Reducing the metabolic burden of rRNA synthesis promotes healthy longevity in Caenorhabditis elegans," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    3. Judith Dönig & Hannah Mende & Jimena Davila Gallesio & Kristina Wagner & Paul Hotz & Kathrin Schunck & Tanja Piller & Soraya Hölper & Sara Uhan & Manuel Kaulich & Matthias Wirth & Ulrich Keller & Geor, 2023. "Characterization of nucleolar SUMO isopeptidases unveils a general p53-independent checkpoint of impaired ribosome biogenesis," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    4. James C. Murphy & Elena M. Harrington & Sophie Schumann & Elton J. R. Vasconcelos & Timothy J. Mottram & Katherine L. Harper & Julie L. Aspden & Adrian Whitehouse, 2023. "Kaposi’s sarcoma-associated herpesvirus induces specialised ribosomes to efficiently translate viral lytic mRNAs," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    5. Hua Yu & Zhen Sun & Tianyu Tan & Hongru Pan & Jing Zhao & Ling Zhang & Jiayu Chen & Anhua Lei & Yuqing Zhu & Lang Chen & Yuyan Xu & Yaxin Liu & Ming Chen & Jinghao Sheng & Zhengping Xu & Pengxu Qian &, 2021. "rRNA biogenesis regulates mouse 2C-like state by 3D structure reorganization of peri-nucleolar heterochromatin," Nature Communications, Nature, vol. 12(1), pages 1-21, December.

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