Clock-controlled mir-142-3p can target its activator, Bmal1

BMC Molecular Biology

Xiaozhong Peng¹  Hui Pan²  Bin Yin¹  Lan Zhou³  Peng Zhang³  Xiaochao Tan¹ 

[1] State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China;Department of Endocrinology, Peking Union Medical Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China;Department of Physiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China

关键词: Circadian clock;    Bmal1;    mir-142-3p;   

Others  :  1091609
DOI  :  10.1186/1471-2199-13-27

 received in 2012-04-26, accepted in 2012-08-23,  发布年份 2012

【 摘 要 】

Background

microRNAs (miRNAs) are shown to be involved in the regulation of circadian clock. However, it remains largely unknown whether miRNAs can regulate the core clock genes (Clock and Bmal1).

Results

In this study, we found that mir-142-3p directly targeted the 3’UTR of human BMAL1 and mouse Bmal1. The over-expression (in 293ET and NIH3T3 cells) and knockdown (in U87MG cells) of mir-142-3p reduced and up-regulated the Bmal1/BMAL1 mRNA and protein levels, respectively. Moreover, the expression level of mir-142-3p oscillated in serum-shocked NIH3T3 cells and the results of ChIP and luciferase reporter assays suggested that the expression of mir-142-3p was directly controlled by CLOCK/BMAL1 heterodimers in NIH3T3 cells.

Conclusions

Our study demonstrates that mir-142-3p can directly target the 3’UTR of Bmal1. In addition, the expression of mir-142-3p is controlled by CLOCK/BMAL1 heterodimers, suggesting a potential negative feedback loop consisting of the miRNAs and the core clock genes. These findings open new perspective for studying the molecular mechanism of circadian clock.

【 授权许可】

   
2012 Tan et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Storch KF, Paz C, Signorovitch J, Raviola E, Pawlyk B, Li T, Weitz CJ: Intrinsic circadian clock of the mammalian retina: importance for retinal processing of visual information. Cell 2007, 130(4):730-741.
• [2]Sahar S, Sassone-Corsi P: Metabolism and cancer: the circadian clock connection. Nat Rev Cancer 2009, 9(12):886-896.
• [3]Lamia KA, Storch KF, Weitz CJ: Physiological significance of a peripheral tissue circadian clock. Proc Natl Acad Sci U S A 2008, 105(39):15172-15177.
• [4]Bunger MK, Wilsbacher LD, Moran SM, Clendenin C, Radcliffe LA, Hogenesch JB, Simon MC, Takahashi JS, Bradfield CA: Mop3 is an essential component of the master circadian pacemaker in mammals. Cell 2000, 103(7):1009-1017.
• [5]Gekakis N, Staknis D, Nguyen HB, Davis FC, Wilsbacher LD, King DP, Takahashi JS, Weitz CJ: Role of the CLOCK protein in the mammalian circadian mechanism. Science 1998, 280(5369):1564-1569.
• [6]Takahashi JS, Hong HK, Ko CH, McDearmon EL: The genetics of mammalian circadian order and disorder: implications for physiology and disease. Nat Rev Genet 2008, 9(10):764-775.
• [7]Ripperger JA, Schibler U: Rhythmic CLOCK-BMAL1 binding to multiple E-box motifs drives circadian Dbp transcription and chromatin transitions. Nat Genet 2006, 38(3):369-374.
• [8]DeBruyne JP, Weaver DR, Reppert SM: CLOCK and NPAS2 have overlapping roles in the suprachiasmatic circadian clock. Nat Neurosci 2007, 10(5):543-545.
• [9]Debruyne JP, Noton E, Lambert CM, Maywood ES, Weaver DR, Reppert SM: A clock shock: mouse CLOCK is not required for circadian oscillator function. Neuron 2006, 50(3):465-477.
• [10]Sangoram AM, Saez L, Antoch MP, Gekakis N, Staknis D, Whiteley A, Fruechte EM, Vitaterna MH, Shimomura K, King DP, et al.: Mammalian circadian autoregulatory loop: a timeless ortholog and mPer1 interact and negatively regulate CLOCK-BMAL1-induced transcription. Neuron 1998, 21(5):1101-1113.
• [11]Preitner N, Damiola F, Lopez-Molina L, Zakany J, Duboule D, Albrecht U, Schibler U: The orphan nuclear receptor REV-ERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator. Cell 2002, 110(2):251-260.
• [12]Xu S, Witmer PD, Lumayag S, Kovacs B, Valle D: MicroRNA (miRNA) transcriptome of mouse retina and identification of a sensory organ-specific miRNA cluster. J Biol Chem 2007, 282(34):25053-25066.
• [13]Cheng HY, Papp JW, Varlamova O, Dziema H, Russell B, Curfman JP, Nakazawa T, Shimizu K, Okamura H, Impey S: microRNA modulation of circadian-clock period and entrainment. Neuron 2007, 54(5):813-829.
• [14]Nagel R, Clijsters L, Agami R: The miRNA-192/194 cluster regulates the Period gene family and the circadian clock. FEBS J 2009, 276(19):5447-5455.
• [15]Kadener S, Menet JS, Sugino K, Horwich MD, Weissbein U, Nawathean P, Vagin VV, Zamore PD, Nelson SB, Rosbash M: A role for microRNAs in the Drosophila circadian clock. Genes Dev 2009, 23(18):2179-2191.
• [16]Zhou W, Li Y, Wang X, Wu L, Wang Y: MiR-206-mediated dynamic mechanism of the mammalian circadian clock. BMC Syst Biol 2011, 5(1):141. BioMed Central Full Text
• [17]Shende VR, Goldrick MM, Ramani S, Earnest DJ: Expression and rhythmic modulation of circulating microRNAs targeting the clock gene Bmal1 in mice. PLoS One 2011, 6(7):e22586.
• [18]Kojima S, Shingle DL, Green CB: Post-transcriptional control of circadian rhythms. J Cell Sci 2011, 124(Pt 3):311-320.
• [19]Lee Y, Chen R, Lee HM, Lee C: Stoichiometric relationship among clock proteins determines robustness of circadian rhythms. J Biol Chem 2011, 286(9):7033-7042.
• [20]Saus E, Soria V, Escaramis G, Vivarelli F, Crespo JM, Kagerbauer B, Menchon JM, Urretavizcaya M, Gratacos M, Estivill X: Genetic variants and abnormal processing of pre-miR-182, a circadian clock modulator, in major depression patients with late insomnia. Hum Mol Genet 2010, 19(20):4017-4025.
• [21]Huang B, Zhao J, Lei Z, Shen S, Li D, Shen GX, Zhang GM: Feng ZH: miR-142–3p restricts cAMP production in CD4 + CD25- T cells and CD4 + CD25+ TREG cells by targeting AC9 mRNA. EMBO Rep 2009, 10(2):180-185.
• [22]Sutton GM, Begriche K, Kumar KG, Gimble JM, Perez-Tilve D, Nogueiras R, McMillan RP, Hulver MW, Tschop MH, Butler AA: Central nervous system melanocortin-3 receptors are required for synchronizing metabolism during entrainment to restricted feeding during the light cycle. FASEB J 2009, 24(3):862-872.
• [23]Yan J, Wang H, Liu Y, Shao C: Analysis of gene regulatory networks in the mammalian circadian rhythm. PLoS Comput Biol 2008, 4(10):e1000193.
• [24]Chao TF, Zhang Y, Yan XQ, Yin B, Gong YH, Yuan JG, Qiang BQ, Peng XZ: [MiR-9 regulates the expression of CBX7 in human glioma]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2008, 30(3):268-274.
• [25]Chen Y, Liu W, Chao T, Zhang Y, Yan X, Gong Y, Qiang B, Yuan J, Sun M, Peng X: MicroRNA-21 down-regulates the expression of tumor suppressor PDCD4 in human glioblastoma cell T98G. Cancer Lett 2008, 272(2):197-205.
• [26]Gong Y, Yue J, Wu X, Wang X, Wen J, Lu L, Peng X, Qiang B, Yuan J: NSPc1 is a cell growth regulator that acts as a transcriptional repressor of p21Waf1/Cip1 via the RARE element. Nucleic Acids Res 2006, 34(21):6158-6169.
• [27]Chen C, Ridzon DA, Broomer AJ, Zhou Z, Lee DH, Nguyen JT, Barbisin M, Xu NL, Mahuvakar VR, Andersen MR, et al.: Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res 2005, 33(20):e179.
• [28]Balsalobre A, Damiola F, Schibler U: A serum shock induces circadian gene expression in mammalian tissue culture cells. Cell 1998, 93(6):929-937.