An SREBP-responsive microRNA operon contributes to a regulatory loop for intracellular lipid homeostasis.
Cell Metab
; 18(1): 51-61, 2013 Jul 02.
Article
en En
| MEDLINE
| ID: mdl-23823476
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Operón
/
Genes Reguladores
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MicroARNs
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Proteína 2 de Unión a Elementos Reguladores de Esteroles
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Metabolismo de los Lípidos
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Homeostasis
Límite:
Animals
Idioma:
En
Revista:
Cell Metab
Asunto de la revista:
METABOLISMO
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos