Allosteric inhibition of a stem cell RNA-binding protein by an intermediary metabolite
UMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyDocument Type
Journal ArticlePublication Date
2014-06-16Keywords
Allosteric SiteAmino Acid Motifs
Animals
Cell Differentiation
Cell Line, Tumor
Gene Expression Profiling
Gene Expression Regulation
Mice
Molecular Dynamics Simulation
Nerve Tissue ProteinsOleic AcidPluripotent Stem CellsProtein Structure, TertiaryRNA-Binding ProteinsRecombinant ProteinsStearoyl-CoA DesaturaseStem CellsStructure-Activity RelationshipRNA-binding proteinbiochemistrybiophysicsgene expressionmetabolismoligodendrocytepost-transcriptional regulationstructural biologyBiochemistryBiochemistry, Biophysics, and Structural BiologyBiophysicsGenetics and GenomicsGenomicsStructural Biology
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Show full item recordAbstract
Gene expression and metabolism are coupled at numerous levels. Cells must sense and respond to nutrients in their environment, and specialized cells must synthesize metabolic products required for their function. Pluripotent stem cells have the ability to differentiate into a wide variety of specialized cells. How metabolic state contributes to stem cell differentiation is not understood. In this study, we show that RNA-binding by the stem cell translation regulator Musashi-1 (MSI1) is allosterically inhibited by 18-22 carbon omega-9 monounsaturated fatty acids. The fatty acid binds to the N-terminal RNA Recognition Motif (RRM) and induces a conformational change that prevents RNA association. Musashi proteins are critical for development of the brain, blood, and epithelium. We identify stearoyl-CoA desaturase-1 as a MSI1 target, revealing a feedback loop between omega-9 fatty acid biosynthesis and MSI1 activity. We propose that other RRM proteins could act as metabolite sensors to couple gene expression changes to physiological state.Source
Elife. 2014 Jun 16;3:e02848. doi: 10.7554/eLife.02848. Link to article on publisher's siteDOI
10.7554/eLife.02848Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39757PubMed ID
24935936Notes
First author Carina C. Clingman is a doctoral student in the Biochemistry and Molecular Pharmacology Program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.
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© 2014, Clingman et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
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Except where otherwise noted, this item's license is described as <p>© 2014, Clingman et al. This article is distributed under the terms of the <a href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</a>, which permits unrestricted use and redistribution provided that the original author and source are credited.</p>
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