Transcriptional autoregulation and inhibition of mRNA translation of aminoacid regulator gene cpcA of filamentous fungus Aspergillus nidulans

The CPCA protein of the filamentous fungus Aspergillus nidulans is a member of the c-jun-like transcriptional activator family. It acts as central tra nscription factor of the cross-pathway regulatory network of amino acid bio synthesis and is functionally exchangeable for the general control transcri ptional activator Gcn4p of Saccharomyces cerevisiae. In contrast to GCN4, e xpression of cpcA is strongly regulated by two equally important mechanisms with additive effects that lead to a fivefold increased CPCA protein amoun t under amino acid starvation conditions. One component of cpcA regulation involves a transcriptional autoregulatory mechanism via a CPCA recognition element (CPRE) in the cpcA promoter that causes a sevenfold increased cpcA mRNA level when cells are starved for amino acids. Point mutations in the C PRE cause a constitutively low mRNA level of cpcA and a halved protein leve l when amino acids are limited. Moreover, two upstream open reading frames (uORFs) in the 5 ' region of the cpcA mRNA are important for a translationa l regulatory mechanism. Destruction of both short uORFs results in a sixfol d increased CPCA protein level under nonstarvation conditions and a 10-fold increase under starvation conditions. Mutations in both the CPRE and uORF regulatory elements lead to an intermediate effect, with a low cpcA mRNA le vel but a threefold increased CPCA protein level independent of amino acid availability. These data argue for a combined regulation of cpcA that inclu des a translational regulation like that of yeast GCN4 as well as a transcr iptional regulation like that of the mammalian jun and fos genes.