A1 Refereed original research article in a scientific journal

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




AuthorsYing Liu, Jaakko Mattila, Sami Ventelä, Leena Yadav, Wei Zhang, Nicole Lamichane, Jari Sundström, Otto Kauko, Reidar Grénman, Markku Varjosalo, Jukka Westermarck, Ville Hietakangas

PublisherCELL PRESS

Publication year2017

JournalDevelopmental Cell

Journal name in sourceDEVELOPMENTAL CELL

Journal acronymDEV CELL

Volume43

Issue2

First page 240

Last page252

Number of pages18

ISSN1534-5807

eISSN1878-1551

DOIhttps://doi.org/10.1016/j.devcel.2017.09.022(external)


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.



Last updated on 2024-26-11 at 15:55