UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Date

6-16-2014

Document Type

Article

Subjects

Allosteric Site; Amino Acid Motifs; Animals; Cell Differentiation; Cell Line, Tumor; Gene Expression Profiling; Gene Expression Regulation; Mice; Molecular Dynamics Simulation; Nerve Tissue Proteins; Oleic Acid; Pluripotent Stem Cells; Protein Structure, Tertiary; RNA-Binding Proteins; Recombinant Proteins; Stearoyl-CoA Desaturase; Stem Cells; Structure-Activity Relationship

Disciplines

Biochemistry | Biochemistry, Biophysics, and Structural Biology | Biophysics | Genetics and Genomics | Genomics | Structural Biology

Abstract

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.

Rights and Permissions

Citation: Elife. 2014 Jun 16;3:e02848. doi: 10.7554/eLife.02848. Link to article on publisher's site

DOI of Published Version

10.7554/eLife.02848

Comments

© 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.

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.

Related Resources

Link to Article in PubMed

Keywords

RNA-binding protein, biochemistry, biophysics, gene expression, metabolism, oligodendrocyte, post-transcriptional regulation, structural biology

Journal Title

eLife

PubMed ID

24935936

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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