Ire1-Mediated Unfolded Protein Response and Other Biological Phenomena in Ascomycota Yeasts and Filamentous Fungi.
Ikhrami Mohamad Aji MA, Kimata Yukio Y
Upon dysfunction of the endoplasmic reticulum (ER), namely ER stress, eukaryotic cells commonly change their gene expression profile, resulting in enhanced ER functions. This cytoprotective response is called the unfolded protein response (UPR), whose molecular mechanism was first elucidated in pioneering studies using Saccharomyces cerevisiae. Ire1 is a transmembrane endoribonuclease that acts as an ER stress sensor. While Ire1-dependent unconventional splicing of mRNA encoding Hac1, the transcription factor responsible for UPR, was discovered in the 1990s, the precise mechanisms regulating their production and activation remain under investigation. Studies on Ire1 and Hac1 in other ascomycetes have also advanced, partly from the perspectives of clinical science and industrial applications, thereby uncovering some significant functional differences from those in S. cerevisiae. For instance, many ascomycete species other than S. cerevisiae likely perform regulated Ire1-dependent decay (RIDD), in which mRNAs encoding ER-client proteins are digested to mitigate ER stress. In certain species, Ire1 may preferentially shift its output toward HAC1 mRNA splicing or RIDD, depending on the type of stimulus. This review article provides an overview of classic and recent findings on the regulation and function of Ire1 and its target mRNAs in various ascomycete species.