title: mTOR associates with TFIIIC, is found at tRNA and 5S rRNA genes, and targets their repressor Maf1.
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.
authors.affiliation: Beatson Institute for Cancer Research, Glasgow G61 1BD, United Kingdom.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Kantidakis
authors.forename: Ben A
authors.initials: BA
authors.lastname: Ramsbottom
authors.forename: Joanna L
authors.initials: JL
authors.lastname: Birch
authors.forename: Sarah N
authors.initials: SN
authors.lastname: Dowding
authors.forename: Robert J
authors.initials: RJ
authors.lastname: White
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012320:RNA Polymerase III / Q000378:metabolism; D012341:RNA, Ribosomal, 5S / Q000235:genetics* / Q000378:metabolism*; D012343:RNA, Transfer / Q000235:genetics* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000737:chemistry; D058570:TOR Serine-Threonine Kinases; D019474:Transcription Factors, TFIII / Q000378:metabolism*; D000098832:Transcription Factor TFIIIC
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C520535:MAF1 protein, human; D012341:RNA, Ribosomal, 5S; D011994:Recombinant Proteins; D012097:Repressor Proteins; D019474:Transcription Factors, TFIII; D000098832:Transcription Factor TFIIIC; D012694:Serine; D012343:RNA, Transfer; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D012320:RNA Polymerase III