A regulatory role for microRNA 33* in controlling lipid metabolism gene expression.

Abstract:

:hsa-miR-33a and hsa-miR-33b, intronic microRNAs (miRNAs) located within the sterol regulatory element-binding protein 2 and 1 genes (Srebp-2 and -1), respectively, have recently been shown to regulate lipid homeostasis in concert with their host genes. Although the functional role of miR-33a and -b has been highly investigated, the role of their passenger strands, miR-33a* and -b*, remains unclear. Here, we demonstrate that miR-33a* and -b* accumulate to steady-state levels in human, mouse, and nonhuman primate tissues and share a similar lipid metabolism target gene network as their sister strands. Analogous to miR-33, miR-33* represses key enzymes involved in cholesterol efflux (ABCA1 and NPC1), fatty acid metabolism (CROT and CPT1a), and insulin signaling (IRS2). Moreover, miR-33* also targets key transcriptional regulators of lipid metabolism, including SRC1, SRC3, NFYC, and RIP140. Importantly, inhibition of either miR-33 or miR-33* rescues target gene expression in cells overexpressing pre-miR-33. Consistent with this, overexpression of miR-33* reduces fatty acid oxidation in human hepatic cells. Altogether, these data support a regulatory role for the miRNA* species and suggest that miR-33 regulates lipid metabolism through both arms of the miR-33/miR-33* duplex.

journal_name

Mol Cell Biol

authors

Goedeke L,Vales-Lara FM,Fenstermaker M,Cirera-Salinas D,Chamorro-Jorganes A,Ramírez CM,Mattison JA,de Cabo R,Suárez Y,Fernández-Hernando C

doi

10.1128/MCB.01714-12

subject

Has Abstract

pub_date

2013-06-01 00:00:00

pages

2339-52

issue

11

eissn

0270-7306

issn

1098-5549

pii

MCB.01714-12

journal_volume

33

pub_type

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