miR-211 Is a Prosurvival MicroRNA that Regulates chop Expression in a PERK-Dependent Manner
Autor: | Ekaterina Bobrovnikova-Marjon, Dariusz Pytel, Jake A. Kushner, Brian Frederick, Hui Zheng, Constantinos Koumenis, J. Alan Diehl, Nancy L. Maas, Nilesh Chitnis, Lewis A. Chodosh, Dhruv K. Pant, Serge Y. Fuchs |
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Rok vydání: | 2012 |
Předmět: |
Cell Survival
Apoptosis CHOP Biology Methylation Article Histones Mice eIF-2 Kinase Cell Line Tumor Histone methylation microRNA Animals Humans Phosphorylation Promoter Regions Genetic Molecular Biology Transcription factor Cells Cultured Mice Knockout Transcription Factor CHOP Regulation of gene expression Reverse Transcriptase Polymerase Chain Reaction ATF6 Cell Biology Fibroblasts Embryo Mammalian Endoplasmic Reticulum Stress Activating Transcription Factor 4 DNA-Binding Proteins MicroRNAs Gene Expression Regulation NIH 3T3 Cells Cancer research Unfolded protein response Thapsigargin HeLa Cells Transcription Factors |
Zdroj: | Molecular Cell. 48:353-364 |
ISSN: | 1097-2765 |
Popis: | MicroRNAs typically function at the level of posttranscriptional gene silencing within the cytoplasm; however, increasing evidence suggests that they may also function in nuclear, Argonaut-containing complexes, to directly repress target gene transcription. We have investigated the role of microRNAs in mediating endoplasmic reticulum (ER) stress responses. ER stress triggers the activation of three signaling molecules: Ire-1α/β, PERK, and ATF6, whose function is to facilitate adaption to the ensuing stress. We demonstrate that PERK induces miR-211, which in turn attenuates stress-dependent expression of the proapoptotic transcription factor chop/gadd153. MiR-211 directly targets the proximal chop/gadd153 promoter, where it increases histone methylation and represses chop expression. Maximal chop accumulation ultimately correlates with miR-211 downregulation. Our data suggest a model in which PERK-dependent miR-211 induction prevents premature chop accumulation and thereby provides a window of opportunity for the cell to re-establish homeostasis prior to apoptotic commitment. |
Databáze: | OpenAIRE |
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