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

263 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

Fingerprint

Peroxisome Proliferator-Activated Receptors
MicroRNAs
Orphan Nuclear Receptors
Gene Expression
Antisense Oligonucleotides
Liver
Metabolic Networks and Pathways
Lipid Metabolism
Half-Life
Hepatocytes
Up-Regulation
Down-Regulation
Cholesterol
Messenger RNA
Proteins

Keywords

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

Cite this

David, G., Le Martelot, G., Vejnar, C. E., Gerlach, D., Schaad, O., Fleury-Olela, F., ... 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
David, Gatfield; ; Le Martelot, Gwendal ; Vejnar, Charles E. ; Gerlach, Daniel ; Schaad, Olivier ; Fleury-Olela, Fabienne ; Ruskeepää, Anna-Liisa ; Oresic, Matej ; Esau, Christine C. ; Zdobnov, Evgeny M. ; Schibler, Ueli. / Integration of microRNA miR-122 in hepatic circadian gene expression. In: Genes and Development. 2009 ; Vol. 23, No. 11. pp. 1313-1326.
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David, G, Le Martelot, G, Vejnar, CE, Gerlach, D, Schaad, O, Fleury-Olela, F, Ruskeepää, A-L, Oresic, M, Esau, CC, Zdobnov, EM & Schibler, U 2009, 'Integration of microRNA miR-122 in hepatic circadian gene expression', Genes and Development, vol. 23, no. 11, pp. 1313-1326. https://doi.org/10.1101/gad.1781009

Integration of microRNA miR-122 in hepatic circadian gene expression. / David, Gatfield; Le Martelot, Gwendal; Vejnar, Charles E.; Gerlach, Daniel; Schaad, Olivier; Fleury-Olela, Fabienne; Ruskeepää, Anna-Liisa; Oresic, Matej; Esau, Christine C.; Zdobnov, Evgeny M.; Schibler, Ueli (Corresponding Author).

In: Genes and Development, Vol. 23, No. 11, 2009, p. 1313-1326.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Integration of microRNA miR-122 in hepatic circadian gene expression

AU - David, Gatfield;

AU - Le Martelot, Gwendal

AU - Vejnar, Charles E.

AU - Gerlach, Daniel

AU - Schaad, Olivier

AU - Fleury-Olela, Fabienne

AU - Ruskeepää, Anna-Liisa

AU - Oresic, Matej

AU - Esau, Christine C.

AU - Zdobnov, Evgeny M.

AU - Schibler, Ueli

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

KW - Circadian

KW - miRNA

KW - miR-122

KW - metabolism

KW - clock

KW - PPAR

U2 - 10.1101/gad.1781009

DO - 10.1101/gad.1781009

M3 - Article

VL - 23

SP - 1313

EP - 1326

JO - Genes and Development

JF - Genes and Development

SN - 0890-9369

IS - 11

ER -

David G, Le Martelot G, Vejnar CE, Gerlach D, Schaad O, Fleury-Olela F et al. Integration of microRNA miR-122 in hepatic circadian gene expression. Genes and Development. 2009;23(11):1313-1326. https://doi.org/10.1101/gad.1781009