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Scientific Article
unige:5601 
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Integration of microRNA miR-122 in hepatic circadian gene expression |
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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 | 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 | |
| Identifiers | DOI: 10.1101/gad.1781009 PMID: 19487572 | |
| Full text |
Article (Published version) (1.3 MB) - Limited access to UNIGE Supplemental Data (8 MB) - Limited access to UNIGE Other version: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701584/?tool=pubmed |
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| Structures | ||
| Research groups | Swiss Institute of Bioinformatics Génomique Evolutionnaire Computationnelle (830) | |
| Citation (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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