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Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling
10:00

Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling

Published on: October 28, 2014

TOR regulates ribosomal protein gene expression via PKA and the Forkhead transcription factor FHL1

Dietmar E Martin1, Alexandre Soulard, Michael N Hall

  • 1Division of Biochemistry, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.

Cell
|December 29, 2004
PubMed

Insights

The target of rapamycin (TOR) pathway regulates ribosome biogenesis via protein kinase A (PKA). This study identifies Forkhead-like transcription factor 1 (FHL1) and its cofactors IFH1 and CRF1 as key players in this nutrient-sensitive signaling mechanism.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Ribosome biogenesis is crucial for cell growth and is tightly regulated by environmental cues.
  • The nutrient-sensitive target of rapamycin (TOR) signaling pathway is a central regulator of cell growth.
  • TOR influences protein kinase A (PKA) localization, but its downstream transcription factors for ribosomal protein (RP) gene regulation remain unidentified.

Purpose of the Study:

  • To elucidate the transcription factors mediating RP gene regulation by the TOR-PKA pathway in yeast.
  • To uncover the signaling mechanism linking environmental sensing to ribosome biogenesis control.

Main Methods:

  • Yeast genetics and molecular biology techniques.
  • Analysis of transcription factor localization and activity.
  • Investigation of protein-protein interactions at RP gene promoters.

Main Results:

  • The Forkhead-like transcription factor FHL1, along with coactivator IFH1 and corepressor CRF1, are essential for TOR/PKA-mediated RP gene transcription.
  • TOR signaling, through PKA, inhibits YAK1 kinase activity and retains CRF1 in the cytoplasm.
  • TOR inactivation leads to YAK1 activation, CRF1 phosphorylation, nuclear accumulation, and subsequent inhibition of RP gene transcription by competing with IFH1 for FHL1 binding.

Conclusions:

  • A novel signaling pathway is described, connecting environmental sensing via TOR/PKA to the regulation of ribosome biogenesis.
  • The interplay between FHL1, IFH1, CRF1, and YAK1 provides a mechanism for controlling RP gene expression in response to nutrient availability.

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