en
Scientific article
English

Integration of microRNA miR-122 in hepatic circadian gene expression

Published inGenes & development, vol. 23, no. 11, p. 1313-1326
Publication date2009
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
  • Animals
  • Circadian Rhythm/genetics/physiology
  • DNA-Binding Proteins/metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genome/genetics
  • Liver/metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs/metabolism
  • Nuclear Receptor Subfamily 1, Group D, Member 1
  • Oligonucleotide Array Sequence Analysis
  • Peroxisome Proliferator-Activated Receptors/metabolism
  • RNA, Messenger/metabolism
  • Receptors, Cytoplasmic and Nuclear/metabolism
  • Time Factors
Citation (ISO format)
GATFIELD, David et al. Integration of microRNA miR-122 in hepatic circadian gene expression. In: Genes & development, 2009, vol. 23, n° 11, p. 1313–1326. doi: 10.1101/gad.1781009
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Identifiers
ISSN of the journal0890-9369
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