title: Nuclear export of the transcription factor NirA is a regulatory checkpoint for nitrate induction in Aspergillus nidulans.
abstract: NirA, the specific transcription factor of the nitrate assimilation pathway of Aspergillus nidulans, accumulates in the nucleus upon induction by nitrate. NirA interacts with the nuclear export factor KapK, which bridges an interaction with a protein of the nucleoporin-like family (NplA). Nitrate induction disrupts the NirA-KapK interaction in vivo, whereas KapK associates with NirA when this protein is exported from the nucleus. A KpaK leptomycin-sensitive mutation leads to inducer-independent NirA nuclear accumulation in the presence of the drug. However, this does not lead to constitutive expression of the genes controlled by NirA. A nirA(c)1 mutation leads to constitutive nuclear localization and activity, remodeling of chromatin, and in vivo binding to a NirA upstream activation sequence. The nirA(c)1 mutation maps in the nuclear export signal (NES) of the NirA protein. The NirA-KapK interaction is nearly abolished in NirA(c)1 and NirA proteins mutated in canonical leucine residues in the NirA NES. The latter do not result in constitutively active NirA protein, which implies that nuclear retention is necessary but not sufficient for NirA activity. The results are consistent with a model in which activation of NirA by nitrate disrupts the interaction of NirA with the NplA/KapK nuclear export complex, thus resulting in nuclear retention, leading to AreA-facilitated DNA binding of the NirA protein and subsequent chromatin remodeling and transcriptional activation.
authors.affiliation: Fungal Genetics and Genomics Unit, Austrian Research Centers and BOKU Vienna, Muthgasse 18, A-1190 Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernreiter
authors.forename: Ana
authors.initials: A
authors.lastname: Ramon
authors.forename: Javier
authors.initials: J
authors.lastname: Fernández-Martínez
authors.forename: Harald
authors.initials: H
authors.lastname: Berger
authors.forename: Lidia
authors.initials: L
authors.lastname: Araújo-Bazan
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Espeso
authors.forename: Robert
authors.initials: R
authors.lastname: Pachlinger
authors.forename: Andreas
authors.initials: A
authors.lastname: Gallmetzer
authors.forename: Ingund
authors.initials: I
authors.lastname: Anderl
authors.forename: Claudio
authors.initials: C
authors.lastname: Scazzocchio
authors.forename: Joseph
authors.initials: J
authors.lastname: Strauss
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D001233:Aspergillus nidulans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001665:Binding Sites / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D028884:Karyopherins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009566:Nitrates / Q000378:metabolism*; D049790:Nuclear Export Signals / Q000187:drug effects; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism; D010641:Phenotype; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017385:Sequence Homology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D000097606:Exportin 1 Protein
chemical_list: D005231:Fatty Acids, Unsaturated; D005656:Fungal Proteins; D028884:Karyopherins; D009566:Nitrates; D049790:Nuclear Export Signals; D028861:Nuclear Pore Complex Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D000097606:Exportin 1 Protein; C071245:NirA protein, Aspergillus nidulans; C038753:leptomycin B