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.
| Identifer | oai:union.ndltd.org:umassmed.edu/oai:escholarship.umassmed.edu:gsbs_diss-1720 |
| Date | 03 September 2014 |
| Creators | Clingman, Carina C. |
| Publisher | eScholarship@UMassChan |
| Source Sets | University of Massachusetts Medical School |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Morningside Graduate School of Biomedical Sciences Dissertations and Theses |
| Rights | Copyright is held by the author, with all rights reserved. |
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