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Integration of microRNA miR-122 in hepatic circadian gene expression

Fleury-Olela, Fabienne
Ruskeepää, Anna-Liisa
Oresic, Matej
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Published in Genes & development. 2009, vol. 23, no. 11, p. 1313-26
Abstract In liver, most metabolic pathways are under circadian control, and hundreds of protein-encoding genes are thus transcribed in a cyclic fashion. Here we show that rhythmic transcription extends to the locus specifying miR-122, a highly abundant, hepatocyte-specific microRNA. Genetic loss-of-function and gain-of-function experiments have identified the orphan nuclear receptor REV-ERBalpha as the major circadian regulator of mir-122 transcription. Although due to its long half-life mature miR-122 accumulates at nearly constant rates throughout the day, this miRNA is tightly associated with control mechanisms governing circadian gene expression. Thus, the knockdown of miR-122 expression via an antisense oligonucleotide (ASO) strategy resulted in the up- and down-regulation of hundreds of mRNAs, of which a disproportionately high fraction accumulates in a circadian fashion. miR-122 has previously been linked to the regulation of cholesterol and lipid metabolism. The transcripts associated with these pathways indeed show the strongest time point-specific changes upon miR-122 depletion. The identification of Pparbeta/delta and the peroxisome proliferator-activated receptor alpha (PPARalpha) coactivator Smarcd1/Baf60a as novel miR-122 targets suggests an involvement of the circadian metabolic regulators of the PPAR family in miR-122-mediated metabolic control.
Keywords AnimalsCircadian Rhythm/genetics/physiologyDNA-Binding Proteins/metabolismGene Expression ProfilingGene Expression RegulationGenome/geneticsLiver/metabolismMaleMiceMice, Inbred C57BLMicroRNAs/metabolismNuclear Receptor Subfamily 1, Group D, Member 1Oligonucleotide Array Sequence AnalysisPeroxisome Proliferator-Activated Receptors/metabolismRNA, Messenger/metabolismReceptors, Cytoplasmic and Nuclear/metabolismTime Factors
PMID: 19487572
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Other version: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701584/?tool=pubmed
Research groups Swiss Institute of Bioinformatics
Génomique Evolutionnaire Computationnelle (830)
(ISO format)
GATFIELD, David et al. Integration of microRNA miR-122 in hepatic circadian gene expression. In: Genes and Development, 2009, vol. 23, n° 11, p. 1313-26. https://archive-ouverte.unige.ch/unige:5601

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Deposited on : 2010-03-25

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