Activation mechanisms of the HAC1-mediated unfolded protein response in filamentous fungi

The unfolded protein response (UPR) is a regulatory pathway activating genes involved in multiple functions related to folding, quality control and transport of secreted proteins. Characterization of the hac1/hacA genes encoding the UPR transcription factors from the filamentous fungi Trichoderma reesei and Aspergillus nidulans is described in this article. The corresponding gene in Saccharomyces cerevisiae is activated through a non-spliceosomal intron-splicing reaction. The T. reesei hac1 and A. nidulans hacA mRNAs undergo an analogous splicing reaction of a 20-nt-long intron during UPR induction. This splicing changes the reading frame of the mRNA and thus could bring in an activation domain to the HACl/HACA proteins. In addition to the non-spliceosomal splicing, the hac1/A mRNAs of the filamentous fungi are truncated at the 5′-flanking region upon UPR induction. An upstream open reading frame is omitted from the mRNAs due to the truncation, and evidence is presented showing that the truncated T. reesei hac1 mRNA is translated more efficiently than a full-length mRNA. This paper reports a novel combination of two different regulatory mechanisms of a transcription factor gene, both operational at the mRNA level.