mTOR binds to the promoters of RNA polymerase I- and III-transcribed genes

Chi Kwan Tsang1, Hui Liu, X F Steven Zheng

  • 1Department of Pharmacology and Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ, USA.

Insights

Mammalian target of rapamycin (mTOR) binds to gene promoters, including ribosomal DNA (rDNA) and transfer RNA (tRNA) genes. This binding is regulated by growth signals and rapamycin, suggesting a conserved role in gene regulation.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Target of rapamycin (TOR) is a crucial regulator of gene expression conserved across species.
  • In yeast, TOR interacts with ribosomal DNA (rDNA) promoters, impacting ribosome biogenesis and tRNA synthesis.
  • The analogous mammalian target of rapamycin (mTOR) function at gene promoters in mammalian cells remains uncharacterized.

Purpose of the Study:

  • To investigate whether mTOR associates with gene promoters in mammalian cells.
  • To determine if this association is conserved and responsive to growth signals and rapamycin.
  • To elucidate mTOR's role in regulating RNA polymerase I- and III-dependent genes.

Main Methods:

  • Detection of mTOR at various gene promoters in human and murine cell lines.
  • Analysis of mTOR promoter association under different growth conditions.
  • Assessment of mTOR promoter binding sensitivity to rapamycin treatment.

Main Results:

  • mTOR was detected at multiple gene promoters in human and murine cells.
  • Key promoters identified include those for rDNA and tRNA genes.
  • mTOR's association with these promoters is modulated by growth signals and rapamycin.

Conclusions:

  • mTOR is involved in gene regulation at promoter regions in mammalian cells.
  • This mechanism appears conserved from yeast to mammals.
  • mTOR plays a role in controlling essential genes for protein synthesis and cell growth.

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