Nuclear Gln3 import is regulated by nitrogen catabolite repression whereas export is specifically regulated by glutamine

Rajendra Rai, Jennifer J. Tate, Karthik Shanmuganatham, Martha M. Howe, David Nelson, Terrance Cooper

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Gln3, a transcription activator mediating nitrogen-responsive gene expression in Saccharomyces cerevisiae, is sequestered in the cytoplasm, thereby minimizing nitrogen catabolite repression (NCR)-sensitive transcription when cells are grown in nitrogen-rich environments. In the face of adverse nitrogen supplies, Gln3 relocates to the nucleus and activates transcription of the NCR-sensitive regulon whose products transport and degrade a variety of poorly used nitrogen sources, thus expanding the cell’s nitrogen-acquisition capability. Rapamycin also elicits nuclear Gln3 localization, implicating Target-of-rapamycin Complex 1 (TorC1) in nitrogen-responsive Gln3 regulation. However, we long ago established that TorC1 was not the sole regulatory system through which nitrogen-responsive regulation is achieved. Here we demonstrate two different ways in which intracellular Gln3 localization is regulated. Nuclear Gln3 entry is regulated by the cell’s overall nitrogen supply, i.e., by NCR, as long accepted. However, once within the nucleus, Gln3 can follow one of two courses depending on the glutamine levels themselves or a metabolite directly related to glutamine. When glutamine levels are high, e.g., glutamine or ammonia as the sole nitrogen source or addition of glutamine analogues, Gln3 can exit from the nucleus without binding to DNA. In contrast, when glutamine levels are lowered, e.g., adding additional nitrogen sources to glutamine-grown cells or providing repressive nonglutamine nitrogen sources, Gln3 export does not occur in the absence of DNA binding. We also demonstrate that Gln3 residues 64–73 are required for nuclear Gln3 export.

Original languageEnglish (US)
Pages (from-to)989-1016
Number of pages28
JournalGenetics
Volume201
Issue number3
DOIs
StatePublished - Nov 1 2015

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Catabolite Repression
Cell Nucleus Active Transport
Glutamine
Nitrogen
Regulon
DNA
Sirolimus
Ammonia

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Nuclear Gln3 import is regulated by nitrogen catabolite repression whereas export is specifically regulated by glutamine. / Rai, Rajendra; Tate, Jennifer J.; Shanmuganatham, Karthik; Howe, Martha M.; Nelson, David; Cooper, Terrance.

In: Genetics, Vol. 201, No. 3, 01.11.2015, p. 989-1016.

Research output: Contribution to journalArticle

Rai, Rajendra ; Tate, Jennifer J. ; Shanmuganatham, Karthik ; Howe, Martha M. ; Nelson, David ; Cooper, Terrance. / Nuclear Gln3 import is regulated by nitrogen catabolite repression whereas export is specifically regulated by glutamine. In: Genetics. 2015 ; Vol. 201, No. 3. pp. 989-1016.
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