Integration of microRNA miR-122 in hepatic circadian gene expressionShow others and affiliations
2009 (English)In: Genes & Development, ISSN 0890-9369, E-ISSN 1549-5477, Vol. 23, no 11, p. 1313-26Article in journal (Refereed) Published
Abstract [en]
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.
Place, publisher, year, edition, pages
Cold Spring Harbor Laboratory Press (CSHL), 2009. Vol. 23, no 11, p. 1313-26
Keywords [en]
Circadian, miRNA, miR-122, metabolism, clock, PPAR
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:oru:diva-70937DOI: 10.1101/gad.1781009ISI: 000266524100006PubMedID: 19487572Scopus ID: 2-s2.0-66149167562OAI: oai:DiVA.org:oru-70937DiVA, id: diva2:1345878
2019-08-262019-08-262019-09-05Bibliographically approved