| First Author | Upton JP | Year | 2012 |
| Journal | Science | Volume | 338 |
| Issue | 6108 | Pages | 818-22 |
| PubMed ID | 23042294 | Mgi Jnum | J:189071 |
| Mgi Id | MGI:5444316 | Doi | 10.1126/science.1226191 |
| Citation | Upton JP, et al. (2012) IRE1alpha cleaves select microRNAs during ER stress to derepress translation of proapoptotic Caspase-2. Science 338(6108):818-22 |
| abstractText | The endoplasmic reticulum (ER) is the primary organelle for folding and maturation of secretory and transmembrane proteins. Inability to meet protein-folding demand leads to "ER stress," and activates IRE1alpha, an ER transmembrane kinase-endoribonuclease (RNase). IRE1alpha promotes adaptation through splicing Xbp1 mRNA or apoptosis through incompletely understood mechanisms. Here, we found that sustained IRE1alpha RNase activation caused rapid decay of select microRNAs (miRs -17, -34a, -96, and -125b) that normally repress translation of Caspase-2 mRNA, and thus sharply elevates protein levels of this initiator protease of the mitochondrial apoptotic pathway. In cell-free systems, recombinant IRE1alpha endonucleolytically cleaved microRNA precursors at sites distinct from DICER. Thus, IRE1alpha regulates translation of a proapoptotic protein through terminating microRNA biogenesis, and noncoding RNAs are part of the ER stress response. |
