| Expression of miR-33 from an SREBP2 intron inhibits cholesterol export and fatty acid oxidation. | |
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MedLine Citation:
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PMID: 20732877 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The regulation of synthesis, degradation, and distribution of lipids is crucial for homeostasis of organisms and cells. The sterol regulatory element-binding protein (SREBP) transcription factor family is post-translationally activated in situations of reduced lipid abundance and activates numerous genes involved in cholesterol, fatty acid, and phospholipid synthesis. In this study, we provide evidence that the primary transcript of SREBP2 contains an intronic miRNA (miR-33) that reduces cellular cholesterol export via inhibition of translation of the cholesterol export pump ABCA1. Notably, miR-33 also inhibits translation of several transcripts encoding proteins involved in fatty acid β-oxidation including CPT1A, HADHB, and CROT, thereby reducing fatty acid degradation. The genetic locus encoding SREBP2 and miR-33 therefore contains a protein that increases lipid synthesis and a miRNA that prevents export and degradation of newly synthesized lipids. These results add an additional layer of complexity to our understanding of lipid homeostasis and might open possibilities for future therapeutic intervention. |
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Authors:
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Isabelle Gerin; Laure-Alix Clerbaux; Olivier Haumont; Nicolas Lanthier; Arun K Das; Charles F Burant; Isabelle A Leclercq; Ormond A MacDougald; Guido T Bommer |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-08-22 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 285 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-25 Completed Date: 2010-11-16 Revised Date: 2011-10-31 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 33652-61 Citation Subset: IM |
Affiliation:
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Laboratory for Physiological Chemistry, de Duve Institute, Université Catholique de Louvain, 1200 Bruxelles, Belgium. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cholesterol / metabolism* Fatty Acids / chemistry* Gene Expression Regulation* Humans Introns* Lentivirus / genetics Male Mice Mice, Inbred C57BL MicroRNAs / biosynthesis* Phospholipids / chemistry Sterol Regulatory Element Binding Protein 2 / genetics* |
| Grant Support | |
ID/Acronym/Agency:
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5P30DK089503/DK/NIDDK NIH HHS; DK51563/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Fatty Acids; 0/MIRN33 microRNA, human; 0/MicroRNAs; 0/Mirn33 microRNA, mouse; 0/Phospholipids; 0/SREBF2 protein, human; 0/Srebf2 protein, mouse; 0/Sterol Regulatory Element Binding Protein 2; 57-88-5/Cholesterol |
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