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Rhythmic expression of miR‐27b‐3p targets the clock gene Bmal1 at the posttranscriptional level in the mouse liver
Author(s) -
Zhang Wenxiang,
Wang Peng,
Chen Siyu,
Zhang Zhao,
Liang Tingming,
Liu Chang
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201500120
Subject(s) - circadian rhythm , biology , microrna , clock , gene expression , circadian clock , microbiology and biotechnology , regulation of gene expression , gene , endocrinology , medicine , genetics
ABSTRACT Circadian clocks orchestrate daily oscillations in mammalian behaviors, physiology, and gene expression. MicroRNAs (miRNAs) play a crucial role in fine‐tuning of the circadian system. However, little is known about the direct regulation of the clock genes by specific miRNAs. In this study, we found that miR‐27b‐3p exhibits rhythmic expression in the metabolic tissues of the mice subjected to constant darkness. MiR‐27b‐3p's expression is induced in livers of unfed and ob/ob mice. In addition, the oscillation phases of miR‐27b‐3p can be reversed by restricted feeding, suggesting a role of peripheral clock in regulating its rhythmicity. Bioinformatics analysis indicated that aryl hydrocarbon receptor nuclear translocator‐like (also known as Bmal1 ) may be a direct target of miR‐27b‐3p. Luciferase reporter assay showed that miR‐27b‐3p suppressed Bmal1 3' UTR activity in a dose‐dependent manner, and mutagenesis of their binding site abolished this suppression. Furthermore, over expression of miR‐27b‐3p dose‐dependently reduced the protein expression levels of BMAL1 and impaired the endogenous BMAL1 and gluconeogenic protein rhythmicity. Collectively, our results suggest that miR‐27b‐3p plays an important role in the posttranscriptional regulation of BMAL1 protein in the liver. MiR‐27b‐3p may serve as a novel node to integrate the circadian clock and energy metabolism.—Zhang, W., Wang, P., Chen, S., Zhang, Z., Liang, T., Liu, C. Rhythmic expression of miR‐27b‐3p targets the clock gene Bmal1 at the posttranscriptional level in the mouse liver. FASEB J. 30, 2151–2160 (2016). www.fasebj.org