Sci. STKE, 5 September 2006
NUTRIENT SENSING TOR on the Promoter
Target of rapamycin (TOR) is a kinase that is a major regulator of cellular responses to nutrient status. In the presence of rapamycin or under conditions of nutrient deprivation conditions, the kinase activity of TOR is inhibited, which decreases protein synthesis and ribosome biogenesis and alters gene expression. Yeast has two TOR encoding genes, Tor1 and Tor2, and the encoded proteins form two complexes called TORC1 and TORC2. Li et al. produced an antibody specific for Tor1 and showed that nutrient deprivation or rapamycin treatment stimulated the exit of Tor1 from the nucleus (in nutrient-replete conditions, TORC1 is both cytosolic and nuclear). The redistribution required an intact nuclear export signal (NES) in Tor1, and rapamycin-stimulated exit was blocked in yeast expressing a mutant form of Crm, a nuclear export protein. Under any conditions, mutation of the second of two nuclear localization signals (NLSs) inhibited nuclear import of Tor1, and nuclear accumulation was blocked in yeast with a mutation in the import protein Srp1. Several genes exhibit TORC1-dependent expression or repression. Yeast expressing the Tor1 mutants that blocked either nuclear export or import continued to exhibit TORC1-mediated regulation of genes transcribed by RNA polymerase II, suggesting that the nuclear activity of TORC1 was not essential for regulation of these genes; rather, this response required regulation of the cytosolic kinase activity of the complex. However, regulation of ribosomal RNA synthesis (specifically the gene encoding the 35S rRNA) was lost in cells expressing the NES mutant. Chromatin immunoprecipitation experiments confirmed that Tor1 and another component of the TORC1 complex, but not components of the TORC2 complex, bound to the 35S rDNA promoter under nutrient-replete conditions, and rapamycin caused the dissociation of Tor1. The binding of Tor1 to the promoter required the helix-turn-helix motif, but not the leucine zipper motifs. Thus, the TORC1 complex appears to have a nuclear function in regulating RNA polymerase I-dependent gene expression and a cytosolic function in regulating RNA polymerase II-dependent gene expression.
H. Li, C. K. Tsang, M. Watkins, P. G. Bertram, X. F. S. Zheng, Nutrient regulates Tor1 nuclear localization and association with rDNA promoter. Nature 442, 1058-1061 (2006). [PubMed]
Citation: TOR on the Promoter. Sci. STKE 2006, tw302 (2006).
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