YEAST 2017

28th International Conference on Yeast Genetics and Molecular Biology (ICYGMB)

August 27 – September 1, 2017
Prague, Czech Republic

Paper ID: 295

From Rags to Riches and Back Again – Nitrogen-Responsive Regulation in S. cerevisiae

Cooper Terrance G

University of Tennessee Health Science Center (USA)


It’s critical for yeast cells to manage internal nitrogen homeostasis in the face of continuous, drastic external transitions. Nitrogen Catabolite Repression (NCR) is the overall regulatory mechanism permitting cells to take full advantage of luxurious nitrogenous environments, yet retain the ability to cope with austere ones; all the while maintaining tight intra-cellular homeostasis. Two types of transcription factors participate: (i) Pathway-specific activators whose binary functioning depends on the concentration of a single inducer, e.g. allophanate for allantoin (DAL) transcription. (ii) Pathway-independent, NCR-sensitive GATA-binding activators, Gln3 and Gat1, which respond to overall intra-cellular nitrogen availability. In nitrogen replete conditions the GATA factors are sequestered in the cytoplasm and NCR-sensitive transcription is minimal. As conditions deteriorate, Gln3 relocates to the nucleus dramatically increasing GATA factor-mediated transcription. NCR-sensitive regulation was originally attributed to TorC1-mediated control of Gln3. However, Gln3 responds to 5 distinct physiological conditions each exhibiting a unique set of regulatory requirements. This, other data and the unique structure of Gln3 allowed us to demonstrate that nitrogen-responsive TorC1 activity only partially accounts for NCR-sensitive regulation. Multiple, previously elusive regulators have now been identified. (i) Uncharged tRNA-activated, Gcn2 kinase-mediated General Amino Acid Control (GAAC). Gcn2 and Gcn4 are required for NCR-sensitive, TorC1-independent nuclear Gln3 localization. Epistasis experiments indicate Gcn2 likely functions upstream of Ure2. Bmh1/2, also required for nuclear Gln3 localization, likely function downstream. Interestingly, overall Gln3 phosphorylation levels decrease upon loss of Gcn2, Gcn4 or Bmh1/2. Further, nuclear import is more complex than previously appreciated and likely occurs in multiple steps. (ii) TorC1 and Gcn2, acting in opposition, are augmented by a third level of intra-nuclear regulation. In high glutamine, Gln3 exits from the nucleus in the absence of binding to its GATA targets in NCR-sensitive promoters. In contrast, as glutamine levels decrease, GATA binding becomes requisite for Gln3 to exit from the nucleus. The concerted actions of these multiple regulatory components impressively illustrate how NCR effectively manages intra-cellular homeostasis in the face of extra-cellular nitrogen environment transitions. GM35642-27.

Nitrogen catabolite repression, Gln3, Ure2, Gcn2, Gcn4, TorC1, rapamycin, nuclear import, nitrogen environments
Presented as:
  CL Closing lecture in Keynote Lectures

Institute of Microbiology

YEAST 2017
28th International Conference on Yeast Genetics and Molecular Biology (ICYGMB)

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