2013
DOI: 10.1016/j.cmet.2013.06.010
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An SREBP-Responsive microRNA Operon Contributes to a Regulatory Loop for Intracellular Lipid Homeostasis

Abstract: 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 micro-RNA locus that is activated directly by SREBP-2. Two of the encoded miRs, miR-182 and miR-96, negatively regulate expression of Fbxw7 and Insig-2 respectively, and both are known to negatively affect nuclear SREBP accumulation. Direct manipulation of this miR pathway alters nuclear SREBP levels an… Show more

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Cited by 102 publications
(112 citation statements)
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“…These results demonstrated that proteins involved in blocking SreBPs transport and nuclear SreBPs degradation all decreased in livers of mice after 28-day exposure to PFOA, indicating the activation of the SreBP maturation pathway. earlier research determined that a SreBP-controlling mirNA cluster, mir-183-96-182, was involved in a regulatory loop intermediated by SreBP maturation (Jeon et al 2013). using TaqMan mirNA assay, we also found a significant increase in the expression level of the mir-183-96-182 cluster (Fig.…”
Section: Pfoa Changed Lipid Content and Activated Ppars In Mouse Livermentioning
confidence: 97%
“…These results demonstrated that proteins involved in blocking SreBPs transport and nuclear SreBPs degradation all decreased in livers of mice after 28-day exposure to PFOA, indicating the activation of the SreBP maturation pathway. earlier research determined that a SreBP-controlling mirNA cluster, mir-183-96-182, was involved in a regulatory loop intermediated by SreBP maturation (Jeon et al 2013). using TaqMan mirNA assay, we also found a significant increase in the expression level of the mir-183-96-182 cluster (Fig.…”
Section: Pfoa Changed Lipid Content and Activated Ppars In Mouse Livermentioning
confidence: 97%
“…SREBP2 directly activates miR-182 and miR-96, which negatively regulate the expression of FBXW7 and INSIG-2, respectively. These genes affect nuclear SREBP levels and endogenous lipid synthesis (29), potentially leading to steatohepatitis (59). Furthermore, several miRNAs directly contribute to liver expression of miR-33 targets, including ABCA1 (target of miR-26, miR-128-2, miR-144) (1, 9, 27, 75), ABCG1 (target of miR-128-2) (1), and CPT1A (target of miR-370) (27).…”
Section: Impact Of Mirnas On Liver Insulin Sensitivity and In The Metmentioning
confidence: 99%
“…Recently, the miR-183/96/182 cluster has been demonstrated to positively regulate cholesterol biosynthesis in liver cells by inhibiting expression of ISIG2 and FBXW7 [51][52][53], which encode factors that negatively regulate SREBF2. Because mature miR-183, miR-96, and miR-182 are either not detected or at very low levels in Dgcr8 +/-NSCs (Supplementary Table S2), it is unlikely that the absence of the miR-183/96/ 182 cluster is responsible for the reduced cholesterol biosynthesis in Dgcr8 -/-NSCs.…”
Section: Dgcr8mentioning
confidence: 99%