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Nutrient regulates Tor1 nuclear localization and association with rDNA promoter

Nature volume 442, pages 1058–1061 (2006)Cite this article

Abstract

TOR is the target of the immunosuppressant rapamycin and a key regulator of cell growth. It modulates diverse cellular processes in the cytoplasm and nucleus1,2,3,4,5, including the expression of amino acid transporters, ribosomal RNAs and ribosomal proteins. Despite considerable recent progress, little is known about the spatial and temporal regulation of TOR signalling, particularly that leading into the nucleus. Here we show that Tor1 is dynamically distributed in the cytoplasm and nucleus in yeast. Tor1 nuclear localization is nutrient dependent and rapamycin sensitive: starvation or treatment with rapamycin causes Tor1 to exit from the nucleus. Tor1 nuclear localization is critical for 35S rRNA synthesis, but not for the expression of amino acid transporters and ribosomal protein genes. We show further that Tor1 is associated with 35S ribosomal DNA (rDNA) promoter chromatin in a rapamycin- and starvation-sensitive manner; this association is necessary for 35S rRNA synthesis and cell growth. These results indicate that the spatial regulation of TOR complex 1 (TORC1) might be involved in differential control of its target genes. TOR is known as a classic cytoplasmic kinase that mediates the cytoplasm-to-nucleus signalling by controlling the localization of transcription factors. Our data indicate that TOR might be more intimately involved in gene regulation than previously thought.

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Figure 1: Tor1 is dynamically distributed in the cytoplasm and nucleus in a rapamycin- and nutrient-sensitive manner.
Figure 2: Tor1 nuclear localization is critical for cell growth and 35S rRNA synthesis.
Figure 4: Tor1 binding to the 35S rDNA promoter is important for cell growth and 35S rRNA synthesis.
Figure 3: Tor1 binds to the 35S rDNA promoter in a rapamycin-sensitive manner.

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Acknowledgements

We thank J. H. Cho for generating the KOG1-MYC9 strain, M. Rout and S. Wente for advice on the purification of yeast nuclei, and H. Sesaki and R. Jensen for Tim23 antibody. This work was supported by an NIH grant to X.F.S.Z. Author Contributions The immunofluorescence experiments were performed by C.K.T. and M.W. Mutagenesis and rapamycin sensitivity assays were performed by H.L. and M.W. Subcellular fractionation, northern blotting and 35S rRNA assays were performed by H.L. ChIP assays were performed by C.K.T. and H.L. Tor1 antibody was generated and characterized by P.G.B. The data were analyzed and interpreted by H.L., C.K.T., M.W., P.G.B. and X.F.S.Z. The data images for the figures were prepared by H.L., C.K.T., M.W. and P.G.B. The manuscript was written by H.L., C.K.T. and X.F.S.Z.

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  1. Hong Li, Chi Kwan Tsang and Marcus Watkins: *These authors contributed equally to this work

Authors and Affiliations

  1. Department of Pharmacology, Robert Wood Johnson Medical School, 675 Hoes Lane, New Jersey, 08854, Piscataway, USA

    Hong Li, Chi Kwan Tsang & X. F. Steven Zheng

  2. Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, Missouri, 63110, St Louis, USA

    Marcus Watkins & Paula G. Bertram

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  1. Hong Li
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Correspondence to X. F. Steven Zheng.

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Li, H., Tsang, C., Watkins, M. et al. Nutrient regulates Tor1 nuclear localization and association with rDNA promoter. Nature 442, 1058–1061 (2006). https://doi.org/10.1038/nature05020

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