The transcription factor HACA mediates the unfolded protein response in Aspergillus niger, and up-regulates its own transcription

The unfolded protein response (UPR) involves a complex signalling pathway in which the transcription factor HACA plays a central role. Here we report the cloning and characterisation of the hacA gene and its product from Aspergillus niger. ER (endoplasmic reticulum) stress results in the splicing of an unconventional 20-nt intron from the A. niger hacA mRNA, and is associated with truncation of the 5'-end of the hacA mRNA by 230 nt. In this study the UPR was triggered by over expressing tissue plasminogen activator (t-PA), and by treatment of mycelia with dithiothreitol (DTT) or tunicamycin. Overexpression of the processed form of hacA not only led to the up-regulation of bipA, cypB and pdiA -mimicking the UPR-but also led to the up-regulation of the hacA gene itself. In vitro binding assays confirmed that the HACA protein binds to the promoters of genes encoding ER-localised chaperones and foldases, and to the promoter of the hacA gene itself. Finally, a GFP-HACA fusion was shown to localise in the nucleus.