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首页> 外文期刊>Cell metabolism >An SREBP-responsive microRNA operon contributes to a regulatory loop for intracellular lipid homeostasis
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An SREBP-responsive microRNA operon contributes to a regulatory loop for intracellular lipid homeostasis

机译：SREBP反应性microRNA操纵子有助于细胞内脂质稳态的调节环。

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Sterol regulatory element-binding proteins (SREBPs) have evolved as a focal point for linking lipid synthesis with other pathways that regulate cell growth and survival. Here, we have uncovered a polycistrionic microRNA (miRNA) locus that is activated directly by SREBP-2. Two of the encoded miRNAs, miR-182 and miR-96, negatively regulate the expression of Fbxw7 and Insig-2, respectively, and both are known to negatively affect nuclear SREBP accumulation. Direct manipulation of this miRNA pathway alters nuclear SREBP levels and endogenous lipid synthesis. Thus, we have uncovered a mechanism for the regulation of intracellular lipid metabolism mediated by the concerted action of a pair of miRNAs that are expressed from the same SREBP-2-regulated miRNA locus, and each targets a different protein of the multistep pathway that regulates SREBP function. These studies reveal an miRNA "operon" analogous to the classic model for genetic control in bacterial regulatory systems.
机译：甾醇调节元件结合蛋白（SREBPs）已发展成为将脂质合成与其他调节细胞生长和存活的途径联系起来的焦点。在这里，我们发现了直接由SREBP-2激活的多柠檬酸微RNA（miRNA）基因座。编码的两个miRNA miR-182和miR-96分别负调控Fbxw7和Insig-2的表达，并且已知两者都对核SREBP积累产生负面影响。该miRNA途径的直接操纵改变了核SREBP水平和内源性脂质合成。因此，我们发现了由同一SREBP-2调控的miRNA基因座表达的一对miRNA的协同作用介导的细胞内脂质代谢的调控机制，且每个靶向的多步途径的不同蛋白质均能调节SREBP功能。这些研究揭示了miRNA“操纵子”，类似于细菌调节系统中遗传控制的经典模型。

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