1. Department of Pharmacology, Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, New Jersey 08854, USA
2. Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
3. *These authors contributed equally to this work

Correspondence to: X. F. Steven Zheng¹ Correspondence and requests for materials should be addressed to X.F.S.Z. (Email: zhengst@umdnj.edu).

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 nucleus^{1, 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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