Volume 34, Issue 2, Pages 133-134 (April 2009) Targeting of mRNAs to Their Sites of Unconventional Splicing in the Unfolded Protein Response  David Ron  Molecular Cell  Volume 34, Issue 2, Pages 133-134 (April 2009) DOI: 10.1016/j.molcel.2009.04.003 Copyright © 2009 Elsevier Inc. Terms and Conditions

Figure 1 Recruitment of XBP1/Hac1 mRNA to ER Membranes in Yeast and Mammals (A) In unstressed yeast, inactive IRE1 is distributed throughout the ER membrane. The unspliced Hac1u mRNA is cytosolic and translationally repressed by base-pairing between the 5′ untranslated region (orange) and the intron (later excised by IRE1 at sites indicated by arrowheads). (B) The threat of protein misfolding (ER stress) activates IRE1 and leads to its clustering in mega-foci that attract the translationally repressed Hac1u mRNA by a process that depends on the 3′ bipartite element (3′BE). (C) IRE1-dependent excision of the intron derepresses translation of the spliced Hac1s mRNA and terminates the recruitment process. (D) In unstressed mammalian cells, the unspliced XBP1u mRNA is translated. A hydrophobic region on the nascent peptide (HR2) partitions to lipids and recruits the ribosome nascent-chain complex to the ER. (E) ER stress-induced, IRE1-mediated unconventional splicing alters the reading frame of the spliced XBP1s mRNA, and the encoded protein, lacking HR2, no longer tethers the ribosome nascent-chain complex to the ER. Molecular Cell 2009 34, 133-134DOI: (10.1016/j.molcel.2009.04.003) Copyright © 2009 Elsevier Inc. Terms and Conditions