An SREBP-responsive microRNA operon contributes to a regulatory loop for intracellular lipid homeostasis

Tae Il Jeon, Ryan M. Esquejo, Manuel Roqueta-Rivera, Peter E. Phelan, Young Ah Moon, Subramaniam S. Govindarajan, Christine C. Esau, Timothy F. Osborne

Research output: Contribution to journalArticle

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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 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.

Original languageEnglish (US)
Pages (from-to)51-61
Number of pages11
JournalCell Metabolism
Volume18
Issue number1
DOIs
StatePublished - Jul 2 2013

Fingerprint

Sterol Regulatory Element Binding Proteins
Operon
MicroRNAs
Homeostasis
Lipids
Sterol Regulatory Element Binding Protein 2
Genetic Models
Lipid Metabolism
Cell Survival
Growth

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

Jeon, T. I., Esquejo, R. M., Roqueta-Rivera, M., Phelan, P. E., Moon, Y. A., Govindarajan, S. S., ... Osborne, T. F. (2013). An SREBP-responsive microRNA operon contributes to a regulatory loop for intracellular lipid homeostasis. Cell Metabolism, 18(1), 51-61. https://doi.org/10.1016/j.cmet.2013.06.010

An SREBP-responsive microRNA operon contributes to a regulatory loop for intracellular lipid homeostasis. / Jeon, Tae Il; Esquejo, Ryan M.; Roqueta-Rivera, Manuel; Phelan, Peter E.; Moon, Young Ah; Govindarajan, Subramaniam S.; Esau, Christine C.; Osborne, Timothy F.

In: Cell Metabolism, Vol. 18, No. 1, 02.07.2013, p. 51-61.

Research output: Contribution to journalArticle

Jeon, TI, Esquejo, RM, Roqueta-Rivera, M, Phelan, PE, Moon, YA, Govindarajan, SS, Esau, CC & Osborne, TF 2013, 'An SREBP-responsive microRNA operon contributes to a regulatory loop for intracellular lipid homeostasis', Cell Metabolism, vol. 18, no. 1, pp. 51-61. https://doi.org/10.1016/j.cmet.2013.06.010
Jeon TI, Esquejo RM, Roqueta-Rivera M, Phelan PE, Moon YA, Govindarajan SS et al. An SREBP-responsive microRNA operon contributes to a regulatory loop for intracellular lipid homeostasis. Cell Metabolism. 2013 Jul 2;18(1):51-61. https://doi.org/10.1016/j.cmet.2013.06.010
Jeon, Tae Il ; Esquejo, Ryan M. ; Roqueta-Rivera, Manuel ; Phelan, Peter E. ; Moon, Young Ah ; Govindarajan, Subramaniam S. ; Esau, Christine C. ; Osborne, Timothy F. / An SREBP-responsive microRNA operon contributes to a regulatory loop for intracellular lipid homeostasis. In: Cell Metabolism. 2013 ; Vol. 18, No. 1. pp. 51-61.
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