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

Kantidakis, T., Ramsbottom, B. A., Birch, J. L. , Dowding, S. N. and White, R. J. (2010) mTOR associates with TFIIIC, is found at tRNA and 5S rRNA genes, and targets their repressor Maf1. Proceedings of the National Academy of Sciences of the United States of America, 107(26), pp. 11823-11828. (doi: 10.1073/pnas.1005188107) (PMID:20543138) (PMCID:PMC2900655)

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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

Item Type:Articles
Additional Information:We thank Michael Hall, Eyal Gottlieb, Chris Proud, John Blenis, and David Sabatini for discussions regarding these data. This work was funded by Grant 081977/Z/07/Z from the Wellcome Trust, by a Glasgow University studentship, and by Cancer Research UK.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:White, Prof Robert and Birch, Dr Joanna
Authors: Kantidakis, T., Ramsbottom, B. A., Birch, J. L., Dowding, S. N., and White, R. J.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences
ISSN:0027-8424
ISSN (Online):1091-6490

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
448501Regulation of RNA polymerase III transcription by Maf1 in mammalsRobert WhiteWellcome Trust (WELLCOME)081977/Z/07/ZInstitute of Cancer Sciences