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Dev Cell. 2017 Oct 23;43(2):240-252.e5. doi: 10.1016/j.devcel.2017.09.022.

PWP1 Mediates Nutrient-Dependent Growth Control through Nucleolar Regulation of Ribosomal Gene Expression.

Author information

1
Department of Biosciences, University of Helsinki, 00790 Helsinki, Finland; Institute of Biotechnology, University of Helsinki, 00790 Helsinki, Finland.
2
Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, 20520 Turku, Finland.
3
Institute of Biotechnology, University of Helsinki, 00790 Helsinki, Finland.
4
Department of Pathology, University of Turku, 20520 Turku, Finland; Department of Pathology, Turku University Hospital, 20521 Turku, Finland.
5
Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, 20520 Turku, Finland; Department of Pathology, University of Turku, 20520 Turku, Finland.
6
Department of Otorhinolaryngology - Head and Neck Surgery and Department of Medical Biochemistry and Genetics, University of Turku and Turku University Hospital, 20521 Turku, Finland.
7
Department of Biosciences, University of Helsinki, 00790 Helsinki, Finland; Institute of Biotechnology, University of Helsinki, 00790 Helsinki, Finland. Electronic address: ville.hietakangas@helsinki.fi.

Abstract

Ribosome biogenesis regulates animal growth and is controlled by nutrient-responsive mTOR signaling. How ribosome biogenesis is regulated during the developmental growth of animals and how nutrient-responsive signaling adjusts ribosome biogenesis in this setting have remained insufficiently understood. We uncover PWP1 as a chromatin-associated regulator of developmental growth with a conserved role in RNA polymerase I (Pol I)-mediated rRNA transcription. We further observed that PWP1 epigenetically maintains the rDNA loci in a transcription-competent state. PWP1 responds to nutrition in Drosophila larvae via mTOR signaling through gene expression and phosphorylation, which controls the nucleolar localization of dPWP1. Our data further imply that dPWP1 acts synergistically with mTOR signaling to regulate the nucleolar localization of TFIIH, a known elongation factor of Pol I. Ribosome biogenesis is often deregulated in cancer, and we demonstrate that high PWP1 levels in human head and neck squamous cell carcinoma tumors are associated with poor prognosis.

KEYWORDS:

RNA polymerase I; cancer; development; growth; mTOR; nutrient sensing; ribosome biogenesis

PMID:
29065309
DOI:
10.1016/j.devcel.2017.09.022
[Indexed for MEDLINE]

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