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A CHOP-regulated microRNA controls rhodopsin expression

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 p...

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Detalles Bibliográficos
Autores principales: Behrman, Shannon, Acosta-Alvear, Diego, Walter, Peter
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3063143/
https://www.ncbi.nlm.nih.gov/pubmed/21402790
http://dx.doi.org/10.1083/jcb.201010055
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author Behrman, Shannon
Acosta-Alvear, Diego
Walter, Peter
author_facet Behrman, Shannon
Acosta-Alvear, Diego
Walter, Peter
author_sort Behrman, Shannon
collection PubMed
description 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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spelling pubmed-30631432011-09-21 A CHOP-regulated microRNA controls rhodopsin expression Behrman, Shannon Acosta-Alvear, Diego Walter, Peter J Cell Biol Research Articles 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. The Rockefeller University Press 2011-03-21 /pmc/articles/PMC3063143/ /pubmed/21402790 http://dx.doi.org/10.1083/jcb.201010055 Text en © 2011 Behrman et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Behrman, Shannon
Acosta-Alvear, Diego
Walter, Peter
A CHOP-regulated microRNA controls rhodopsin expression
title A CHOP-regulated microRNA controls rhodopsin expression
title_full A CHOP-regulated microRNA controls rhodopsin expression
title_fullStr A CHOP-regulated microRNA controls rhodopsin expression
title_full_unstemmed A CHOP-regulated microRNA controls rhodopsin expression
title_short A CHOP-regulated microRNA controls rhodopsin expression
title_sort chop-regulated microrna controls rhodopsin expression
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3063143/
https://www.ncbi.nlm.nih.gov/pubmed/21402790
http://dx.doi.org/10.1083/jcb.201010055
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