title: Rhythmic expression of miR-27b-3p targets the clock gene Bmal1 at the posttranscriptional level in the mouse liver.
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, overexpression 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.
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China.
authors.forename: Wenxiang
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China.
authors.forename: Siyu
authors.initials: S
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China tmliang@njnu.edu.cn changliu@njnu.edu.cn.
authors.forename: Tingming
authors.initials: T
authors.lastname: Liang
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China tmliang@njnu.edu.cn changliu@njnu.edu.cn.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
mesh_terms: D020413:3' Untranslated Regions; D056930:ARNTL Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002940:Circadian Rhythm; D005508:Food Deprivation; D005786:Gene Expression Regulation / Q000502:physiology*; D022781:Hepatocytes / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional / Q000502:physiology*
chemical_list: D020413:3' Untranslated Regions; D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse; D035683:MicroRNAs; C540674:Mirn27 microRNA, mouse
keywords: circadian clock; energy metabolism; miRNAs; restricted feeding