XBP isoforms bind each other to shut down the unfolded protein response (arrowhead).

Although most RNA splicing occurs in the nucleus, HAC1 and XBP1 mRNAs are spliced in the cytoplasm during ER stress. On page 565, Yoshida et al. demonstrate that in the case of XBP1 both the unspliced and spliced RNAs produce functional proteins and together the proteins form a feedback system that controls the duration of the stress response.

When unfolded proteins accumulate in the ER, sensor proteins trigger expression of chaperones. One sensor, IRE1, is a membrane-bound RNase located in the ER membrane. IRE1 cleaves XBP1 RNA to produce an mRNA encoding a transcription factor. Although unspliced XBP1, (XBP1[U]), is translated, it is degraded immediately and previously had no known function.

With improved extraction techniques, Yoshida et al. found that XBP1(U) does accumulate in cells and shuttles between the nucleus and...

The Rockefeller University Press
2006
The Rockefeller University Press
2006
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