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Vol. 8, Issue 10, 1845-1862, October 1997
HSP Research Institute, Kyoto Research Park, Shimogyo-ku, Kyoto
600, Japan
An intracellular signaling from the endoplasmic reticulum (ER) to
the nucleus, called the unfolded protein response (UPR), is activated
when unfolded proteins are accumulated in the ER under a variety of
stress conditions ("ER stress"). We and others recently identified
Hac1p/Ern4p as a transcription factor responsible for the UPR in
Saccharomyces cerevisiae. It was further reported that
Hac1p (238 aa) is detected only in ER-stressed cells, and its
expression is mediated by unconventional splicing of
HAC1 precursor mRNA. The splicing replaces the
C-terminal portion of Hac1p; it was proposed that precursor mRNA is
also translated but the putative product of 230 aa is rapidly degraded
by the ubiquitin-proteasome pathway. We have identified and
characterized the same regulated splicing and confirmed its essential
features. Contrary to the above proposal, however, we find that the
238-aa product of mature mRNA and the 230-aa-type protein tested are highly unstable with little or no difference in stability. Furthermore, we demonstrate that the absence of Hac1p in unstressed cells is due to
the lack of translation of precursor mRNA. We conclude that Hac1p is
synthesized as the result of ER stress-induced mRNA splicing, leading
to activation of the UPR.
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