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PWP1 Mediates Nutrient-Dependent Growth Control through Nucleolar Regulation of Ribosomal Gene Expression
- Source :
- Developmental cell. 43(2)
- Publication Year :
- 2016
-
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.
- Subjects :
- 0301 basic medicine
Transcription, Genetic
Ribosome biogenesis
Cell Cycle Proteins
Biology
ta3111
DNA, Ribosomal
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
RNA Polymerase I
Gene expression
RNA polymerase I
Animals
Humans
Phosphorylation
Molecular Biology
Genetics
TOR Serine-Threonine Kinases
Nuclear Proteins
Cell Biology
Ribosomal RNA
Prognosis
RRNA transcription
Chromatin
Cell biology
Elongation factor
Survival Rate
030104 developmental biology
Gene Expression Regulation
Food
Head and Neck Neoplasms
RNA, Ribosomal
Transcription factor II H
Carcinoma, Squamous Cell
Drosophila
Ribosomes
Cell Nucleolus
Developmental Biology
Signal Transduction
Subjects
Details
- ISSN :
- 18781551
- Volume :
- 43
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Developmental cell
- Accession number :
- edsair.doi.dedup.....17cdfc01dae95b89bfb079c510c3b6b1