Mammalian ER stress sensor IRE1β specifically down-regulates the synthesis of secretory pathway proteins

Accumulation of unfolded proteins in the endoplasmic reticulum (ER) causes ER stress. The ER stress sensor inositol requiring enzyme-1beta (IRE1 beta), which is specifically expressed in intestinal epithelial cells, is thought to be involved in translational repression. However, its mechanism of action is not fully understood. Using a reporter that can evaluate and distinguish between translation efficiency in the cytosol and on the ER membrane, we show here that IRE1 beta represses translation on the ER membrane but not in the cytosol, and that this selective repression depends on the RNase activity of IRE1 beta. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.