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Publication : A CHOP-regulated microRNA controls rhodopsin expression.

First Author  Behrman S Year  2011
Journal  J Cell Biol Volume  192
Issue  6 Pages  919-27
PubMed ID  21402790 Mgi Jnum  J:169925
Mgi Id  MGI:4943601 Doi  10.1083/jcb.201010055
Citation  Behrman S, et al. (2011) A CHOP-regulated microRNA controls rhodopsin expression. J Cell Biol 192(6):919-27
abstractText  Using genome-wide microribonucleic acid (microRNA [miRNA]) expression profiling, bioinformatics, and biochemical analyses, we identified miR-708, an endoplasmic reticulum (ER) stress-inducible miRNA whose expression is regulated by the transcription factor CCAAT enhancer-binding protein homologous protein (CHOP) in vertebrates. miR-708 is encoded within an intron of the CHOP-regulated gene Odz4, a member of the highly conserved teneurin family of developmental regulators. Odz4 and mir-708 expression is coregulated by CHOP, and the two transcripts are coexpressed in the brain and eyes of mice, suggesting common physiological functions in these tissues. We validated rhodopsin as a target of miR-708 through loss- and gain-of-function experiments. Together, our data implicate miR-708 in the homeostatic regulation of ER function in mammalian rod photoreceptors, whereby miR-708 may help prevent an excessive rhodopsin load from entering the ER. Hence, miR-708 may function analogously to other unfolded protein response controls that throttle protein influx into the ER to avoid ER stress through mechanisms, such as general translational attenuation by protein kinase RNA-like ER kinase or membrane-bound messenger RNA decay by inositol-requiring enzyme 1.
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