Expression of miR-33 from an SREBP2 Intron Inhibits Cholesterol Export and Fatty Acid Oxidation
Expression of miR-33 from an SREBP2 Intron Inhibits Cholesterol Export and Fatty Acid Oxidation
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DOI：
10.1074/jbc.m110.152090
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发表时间：
2010-10-29
影响因子：
4.8
通讯作者：
Bommer, Guido T.
中科院分区：
文献类型：
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作者：
Gerin, Isabelle;Clerbaux, Laure-Alix;Bommer, Guido T.
脂质的合成、降解和分布的调节对于生物体和细胞的稳态是至关重要的。固醇调节元件结合蛋白（SREBP）转录因子家族在脂质丰度降低的情况下被后激活，并激活参与胆固醇、脂肪酸和磷脂合成的许多基因。在这项研究中，我们提供的证据表明，SREBP 2的主要转录本含有一个内含子miRNA（miR-33），通过抑制胆固醇输出泵ABCA 1的翻译来减少细胞胆固醇输出。值得注意的是，miR-33还抑制编码参与脂肪酸β-氧化的蛋白质（包括CPT 1A、HADHB和CROT）的几种转录物的翻译，从而减少脂肪酸降解。因此，编码SREBP 2和miR-33的基因座含有增加脂质合成的蛋白质和防止新合成的脂质的输出和降解的miRNA。这些结果为我们对脂质稳态的理解增加了额外的复杂性，并可能为未来的治疗干预提供可能性。
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 beta-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.