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Allosteric inhibition of a stem cell RNA-binding protein by an intermediary metabolite
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 special...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4094780/ https://www.ncbi.nlm.nih.gov/pubmed/24935936 http://dx.doi.org/10.7554/eLife.02848 |
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author | Clingman, Carina C Deveau, Laura M Hay, Samantha A Genga, Ryan M Shandilya, Shivender MD Massi, Francesca Ryder, Sean P |
author_facet | Clingman, Carina C Deveau, Laura M Hay, Samantha A Genga, Ryan M Shandilya, Shivender MD Massi, Francesca Ryder, Sean P |
author_sort | Clingman, Carina C |
collection | PubMed |
description | 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 ω-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 ω-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. DOI: http://dx.doi.org/10.7554/eLife.02848.001 |
format | Online Article Text |
id | pubmed-4094780 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-40947802014-07-22 Allosteric inhibition of a stem cell RNA-binding protein by an intermediary metabolite Clingman, Carina C Deveau, Laura M Hay, Samantha A Genga, Ryan M Shandilya, Shivender MD Massi, Francesca Ryder, Sean P eLife Biochemistry 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 ω-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 ω-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. DOI: http://dx.doi.org/10.7554/eLife.02848.001 eLife Sciences Publications, Ltd 2014-06-16 /pmc/articles/PMC4094780/ /pubmed/24935936 http://dx.doi.org/10.7554/eLife.02848 Text en Copyright © 2014, Clingman et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Biochemistry Clingman, Carina C Deveau, Laura M Hay, Samantha A Genga, Ryan M Shandilya, Shivender MD Massi, Francesca Ryder, Sean P Allosteric inhibition of a stem cell RNA-binding protein by an intermediary metabolite |
title | Allosteric inhibition of a stem cell RNA-binding protein by an intermediary metabolite |
title_full | Allosteric inhibition of a stem cell RNA-binding protein by an intermediary metabolite |
title_fullStr | Allosteric inhibition of a stem cell RNA-binding protein by an intermediary metabolite |
title_full_unstemmed | Allosteric inhibition of a stem cell RNA-binding protein by an intermediary metabolite |
title_short | Allosteric inhibition of a stem cell RNA-binding protein by an intermediary metabolite |
title_sort | allosteric inhibition of a stem cell rna-binding protein by an intermediary metabolite |
topic | Biochemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4094780/ https://www.ncbi.nlm.nih.gov/pubmed/24935936 http://dx.doi.org/10.7554/eLife.02848 |
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