mTOR associates with TFIIIC, is found at tRNA and 5S rRNA genes, and targets their repressor Maf1

Theodoros Kantidakis, Ben A. Ramsbottom, Joanna L. Birch, Sarah N. Dowding, Robert J. White

Research output: Contribution to journalArticle

Abstract

Synthesis of tRNA and 5S rRNA by RNA polymerase (pol) III is regulated by the mTOR pathway in mammalian cells. The mTOR kinase localizes to tRNA and 5S rRNA genes, providing an opportunity for direct control. Its presence at these sites can be explained by interaction with TFIIIC, a DNA-binding factor that recognizes the promoters of these genes. TFIIIC contains a TOR signaling motif that facilitates its association with mTOR. Maf1, a repressor that binds and inhibits pol III, is phosphorylated in a mTOR-dependent manner both in vitro and in vivo at serine 75, a site that contributes to its function as a transcriptional inhibitor. Proximity ligation assays confirm the interaction of mTOR with Maf1 and TFIIIC in nuclei. In contrast to Maf1 regulation in yeast, no evidence is found for nuclear export of Maf1 in response to mTOR signaling in HeLa cells. We conclude that mTOR associates with TFIIIC, is recruited to pol III-transcribed genes, and relieves their repression by Maf1.

Original languageEnglish
Pages (from-to)11823-11828
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number26
DOIs
Publication statusPublished - 29 Jun 2010

Keywords

  • Pol III transcription
  • Rapamycin

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