A defined sequence within the 3′ UTR of the areA transcript is sufficient to mediate nitrogen metabolite signalling via accelerated deadenylation

Abstract

Nitrogen metabolism in Aspergillus nidulans is regulated by AREA, a member of the GATA family of transcription factors. One mechanism that modulates AREA activity involves the rapid degradation of the areA transcript when sufficient NH4+ or Gln are available. This signalling mechanism has been shown to require a region of 218 nucleotides within the 3′ untranslated region of areA mRNA. We demonstrate that this region functions independently in a heterologous transcript and acts to accelerate degradation of the poly(A) tail, which in turn leads to rapid transcript degradation in response to the addition of NH4+ or Gln to the growth medium. areA transcript degradation is inhibited by cycloheximide, but this is not a general consequence of translational inhibition. We believe that this is the first reported example in which specific physiological signals, acting through a defined sequence within a transcript, have been shown to promote accelerated poly(A) degradation, which in turn triggers transcript degradation.

Role for RNA-Binding Proteins Implicated in Pathogenic Development of Ustilago maydis

“…Research on RNA-binding proteins in filamentous fungi is still in its infancy, and only a few examples of their biological roles exist (53,65), such as regulation of areA mRNA stability by nitrogen metabolite signaling in Aspergillus nidulans (43,50) or translational regulation by small upstream ORFs in arg-2 and cpcA mRNA from N. crassa and A. nidulans, respectively (19,23). Here, we addressed the roles of the PUM-, KHD-, and RRM-type RNA-binding proteins in U. maydis, through an approach that combined bioinformatics with reverse genetics.…”

Role of Glutamine Synthetase in Nitrogen Metabolite Repression in Aspergillus nidulans

“…Whether these multiple forms of repression operate via a single regulatory pathway involving AreA or whether there are distinct pathways remains to be determined. However, recent evidence suggests that glutamine and glutamate may generate distinct signals that each influence the stability of the areA mRNA through interactions in the 3Ј untranslated region of the areA gene (32) …”

Multiple Nuclear Localization Signals Mediate Nuclear Localization of the GATA Transcription Factor AreA

“…In A. nidulans, the GATA transcription factor AreA is responsible for expression of genes subject to nitrogen metabolite repression (36). When cells are grown under nitrogen limiting conditions, AreA activity is partially derepressed due to increased levels of areA transcription and stability of areA mRNA compared with nitrogen-sufficient conditions (37)(38)(39)(40). AreA activity is further increased during nitrogen limitation due to reduced activity of the NmrA corepressor (41)(42)(43)(44)(45).…”