Integration of microRNA miR-122 in hepatic circadian gene expression

Gatfield; David, Gwendal Le Martelot, Charles E. Vejnar, Daniel Gerlach, Olivier Schaad, Fabienne Fleury-Olela, Anna-Liisa Ruskeepää, Matej Oresic, Christine C. Esau, Evgeny M. Zdobnov, Ueli Schibler (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

266 Citations (Scopus)

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-ERBα 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 Pparβ/δ and the peroxisome proliferator-activated receptor α (PPARα) 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.
Original languageEnglish
Pages (from-to)1313-1326
Number of pages14
JournalGenes and Development
Volume23
Issue number11
DOIs
Publication statusPublished - 2009
MoE publication typeA1 Journal article-refereed

Keywords

  • Circadian
  • miRNA
  • miR-122
  • metabolism
  • clock
  • PPAR

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    David, G., Le Martelot, G., Vejnar, C. E., Gerlach, D., Schaad, O., Fleury-Olela, F., Ruskeepää, A-L., Oresic, M., Esau, C. C., Zdobnov, E. M., & Schibler, U. (2009). Integration of microRNA miR-122 in hepatic circadian gene expression. Genes and Development, 23(11), 1313-1326. https://doi.org/10.1101/gad.1781009