Translational control by the ER transmembrane kinase/ribonuclease IRE1 under ER stress

Under conditions of endoplasmic reticulum (ER) stress, mammalian cells indu ce both translational repression and the unfolded protein response that tra nscriptionally activates genes encoding ER-resident molecular chaperones, T o date, the only known pathway for translational repression in response to ER stress has been the phosphorylation of eIF-2 alpha by the double-strande d RNA-activated protein kinase (PKR) or the transmembrane PKR-like ER kinas e (PERK). Here we report another pathway in which the ER transmembrane kina se/ribonuclease IRE1 beta induces translational repression through 28S ribo somal RNA cleavage in response to ER stress. The evidence suggests that bot h pathways are important for efficient translational repression during the ER stress response.