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    A Feedback Loop Couples Musashi-1 Activity to Omega-9 Fatty Acid Biosynthesis: A Dissertation

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    Authors
    Clingman, Carina C.
    Faculty Advisor
    Sean P. Ryder, PhD
    Academic Program
    Biochemistry and Molecular Pharmacology
    UMass Chan Affiliations
    Biochemistry and Molecular Pharmacology
    Document Type
    Doctoral Dissertation
    Publication Date
    2014-09-03
    Keywords
    Dissertations, UMMS
    Fatty Acids
    Gene Expression Regulation
    RNA
    RNA-Binding Proteins
    Stem Cells
    Fatty Acids
    Gene Expression Regulation
    RNA
    RNA-Binding Proteins
    Stem Cells
    Amino Acids, Peptides, and Proteins
    Biochemistry
    Molecular Biology
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    Abstract
    All living creatures change their gene expression program in response to nutrient availability and metabolic demands. Nutrients and metabolites can directly control transcription and activate second-­‐messenger systems. In bacteria, metabolites also affect post-­‐transcriptional regulatory mechanisms, but there are only a few isolated examples of this regulation in eukaryotes. Here, I present evidence 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. I identify stearoyl-­‐CoA desaturase-­‐1 as a MSI1 target, revealing a feedback loop between ω-­‐9 fatty acid biosynthesis and MSI1 activity. To my knowledge, this is the first example of an RNA-­‐binding protein directly regulated by fatty acid. This finding may represent one of the first examples of a potentially broad network connecting metabolism with post-­‐transcriptional regulation.
    DOI
    10.13028/M2VC8Q
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/32077
    Rights
    Copyright is held by the author, with all rights reserved.
    ae974a485f413a2113503eed53cd6c53
    10.13028/M2VC8Q
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    Morningside Graduate School of Biomedical Sciences Dissertations and Theses

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