Partitioning the transcriptional program induced by rapamycin among the effecters of the Tor proteins

Background: In all organisms, nutrients are primary regulators of signaling pathways that control transcription. In Saccharomyces cerevisiae, the Tor proteins regulate the transcription of genes sensitive to the quality of av ailable nitrogen and carbon sources. Formation of a ternary complex of the immunosuppressant rapamycin, its immunophilin receptor Fpr1p and Tor1p or T or2p results in the nuclear import of several nutrient- and stress-responsi ve transcription factors. Results: We show that treating yeast cells with rapamycin results in a broa der modulation of functionally related gene sets than previously understood . Using chemical epistasis and vector-based global expression analyses, we partition the transcriptional program induced by rapamycin among five effec ters (TAP42, MKS1, URE2, GLN3, GAT1) of the Tor proteins, and identify how the quality of carbon and nitrogen sources impinge upon components of the p rogram. Biochemical data measuring Ure2p phosphorylation coupled with the p artition analysis indicate that there are distinct signaling branches downs tream of the Tor proteins. Conclusions: Whole-genome transcription profiling reveals a striking simila rity between shifting to low-quality carbon or nitrogen sources and treatme nt with rapamycin. These data suggest that the Tor proteins are central sen sors of the quality of carbon and nitrogen sources. Depending on which nutr ient is limited in quality, the Tor proteins can modulate a given pathway d ifferentially. Integrating the partition analysis of the transcriptional pr ogram of rapamycin with the biochemical data, we propose a novel architectu re of Tor protein signaling and of the nutrient-response network, including the identification of carbon discrimination and nitrogen discrimination pa thways.