title: A CHOP-regulated microRNA controls rhodopsin expression.
abstract: 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.
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Behrman
authors.forename: Diego
authors.initials: D
authors.lastname: Acosta-Alvear
authors.forename: Peter
authors.initials: P
authors.lastname: Walter
mesh_terms: D000818:Animals; D001483:Base Sequence; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D007438:Introns; D008565:Membrane Proteins; D051379:Mice; D035683:MicroRNAs / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010802:Phylogeny; D012243:Rhodopsin / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D013312:Stress, Physiological; D014018:Tissue Distribution; D051742:Transcription Factor CHOP / Q000145:classification / Q000235:genetics / Q000378:metabolism*
chemical_list: C497249:DDIT3 protein, human; D008565:Membrane Proteins; D035683:MicroRNAs; D009687:Nuclear Proteins; C113761:Tenm4 protein, mouse; D051742:Transcription Factor CHOP; D012243:Rhodopsin